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1
Cook, Roger, K. Anthony Mizen, and Francoise Person-Dedryver. "Resistance in ryegrasses, Lolium spp., to three European populations of the root-knot nematode, Meloidogyne naasi." Nematology 1, no. 6 (1999): 661–71. http://dx.doi.org/10.1163/156854199508621.
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Abstract Symptoms of Meloidogyne naasi invasion, development and reproduction were compared on 17 cloned ryegrass (Lolium multiflorum and L. perenne) plants, previously classified as susceptible (5 clones) or resistant (12) to a Welsh population. Observations on galling and reproduction confirmed the classification of most clones but some intermediate host status phenotypes were distinguished. Smaller root size at and immediately after inoculation was related to the generally poorer host status of L. perenne clones compared with those of L. multiflorum. Root axes number or size was not related to resistance and susceptiblity in either ryegrass species. In ryegrasses, resistance was expressed by slower nematode development rates, fewer females matured and those that laid eggs were less fecund. Gall numbers at 36 days after inoculation reliably predicted host status. A poor host cultivar of Phleum pratense included some plants on which a few galls with fully fecund females developed. The selected ryegrass clones maintained their phenotype when tested with populations of M. naasi from Belgium and France. Nonetheless, it cannot be concluded from these experiments that there is no heterogeneity for virulence in these nematode populations. Resistance du ray-grass, Lolium spp., a trois populations europeennes du nematode a galle Meloidogyne naasi - Les symptomes causes par la penetration, le developpement et la reproduction de Meloidogyne naasi ont ete compares chez 17 clones de ray-grass (Lolium multiflorum et L. perenne) dont 5 consideres auparavant comme sensibles et 12 comme resistants a une population provenant du Pays de Galles. Les observations relatives a la formation des galles et a la reproduction confirment la qualification de la plupart de ces clones mais quelques phenotypes a statut d'hote intermediaire ont ete detectes. Une longueur de racines plus faible au moment de et immediatement apres l'inoculation est en general correlee au statut d'hote mediocre des clones de L. perenne si on les compare a ceux de L. multiflorum. Le nombre et la taille des racines axiales ne sont correles ni a la resistance ni a la sensibilite chez aucune des especes de ray-grass. La resistance s'exprime chez le ray-grass par le taux plus faible du developpement du nematode, le moindre nombre de femelles matures et une fecondite moins elevee chez celles qui pondent des oeufs. Le nombre de galles releve 36 jours apres l'inoculation permet de predire le statut d'hote de facon fiable. Un cultivar de Phleum pratense a statut d'hote mediocre comportait cependant quelques plants presentant un petit nombre de galles contenant des femelles parfaitement fecondes. Les clones de ray-grass etudies ont conserve leur phenotype lors de tests envers des populations de M. naasi provenant de France et de Belgique. Ces experiences ne permettent cependant pas de conclure qu'il n'existe aucune heterogeneite dans la virulence de ces populations de nematode.
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Gomes, Maria Aparecida, Adriana Oliveira Costa, Washington Luiz Tafuri, and Edward Félix Silva. "An attemp at reversibility and increase of the virulence of axenic strains of Entamoeba histolytica." Revista do Instituto de Medicina Tropical de São Paulo 35, no. 6 (1993): 503–8. http://dx.doi.org/10.1590/s0036-46651993000600005.
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In this study we have tried to verify whether the interaction "in vitro" with bacteria or small pieces of normal hamster liver would modify the pathogenic behavior of axenic strains of E. histolytica: avirulent ones (ICB-32 and ICB-RPS), of attenuated virulence (ICB-CSP and HM1) and of mean virulence (ICB-462). Every attempt to render virulent, recover or increase the virulence of axenic strains of E. histolytica has failed
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Solomon, Aharon, and Itamar Glazer. "Desiccation survival of the entomopathogenic nematode Steinernema feltiae: induction of anhydrobiosis." Nematology 1, no. 1 (1999): 61–68. http://dx.doi.org/10.1163/156854199507983.
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Abstract The present study describes different desiccation tolerance traits of three strains of Steinernema feltiae (IS-6, IS-15, and N8). A slow dehydration regime (pre-conditioning at 97% relative humidity \[RH] for 3 days at 23 degrees C) induced a quiescent anhydrobiosis state in all strains, which enabled them to survive at lower humidities (75% and 85% RH). The IS-6 strain isolated from the Negev desert region of Israel exhibited the best desiccation tolerance. The second best tolerance was observed in the IS-15 strain isolated from Galilee, in the northern part of Israel. The poorest tolerance was exhibited by the N8 strain, which was obtained from Germany. The higher desiccation tolerance of the IS-6 and IS-15 strains was associated with a dispersal response of the aggregated infective juveniles (IJs) at the slow dehydration regime. This allowed the coiled IJs to enter into anhydrobiosis individually, whereas the IJs of the N8 strain remained clumped together. In the present study, the IS-6 strain was chosen to determine the optimal conditions for induction into, and recovery from, anhydrobiosis. A high correlation (r = 0.875, P < 0.05) was found between the survival of individual IJs at 85% RH and the initial numbers of IJs (ranging from 70 to 7700) in the pre-conditioned clump. The same recovery rates of pre-conditioned IJs exposed to 85% RH over a period of 12 days were obtained with either direct immersion in distilled water or immersion in distilled water after 24 h exposure to 100% RH. No significant differences in virulence and ability to penetrate Tenebrio molitor larvae were observed between non-desiccated IJs and rehydrated IJs that had been pre-conditioned and desiccated for 5 days at 85% RH. Survie en etat de deshydratation du nematode entomopathogene Steinernema feltiae: induction de l'anhydrobiose - La presente etude decrit differents aspects de la tolerance a la dessiccation chez trois souches de Steinernema feltiae (IS-6, IS-15 et N8). Une deshydratation lente- preconditionnement a une humidite relative (RH) de 97% pendant 3 jours a 23 degrees C - induit un stade de quiescence anhydrobiotique chez toutes les souches, ce qui les rend capables de survivre a des humidites faibles (RH 75% et 85%). La souche IS-6 isolee dans le desert du Negev (Israel) fait montre de la meilleure tolerance a la dessiccation. Vient ensuite la souche IS-15 isolee en Galilee (partie nord d'Israel). La plus faible tolerance est celle de la souche N8 provenant d'Allemagne. La tolerance plus elevee a la dessiccation des souches IS-6 et IS-15 est associee a une reaction de separation des juveniles infestants (IJ) dans les agregats lors de la deshydratation lente. Cette separation est suivie d'une entree en anhydrobiose des separes, enroules sur eux-memes, tandis que les IJ de la souche N8 restent agglomeres. La souche IS-6 a ete choisie pour determiner les conditions optimales induisant l'anhydrobiose et la sortie de ce stade physiologique. Une forte correlation (r = 0,875, P < 0,05) a ete observee entre la survie des IJ separes a une RH de 85% et la presence d'agregats (comptant 70 a 7700 IJ) au moment du preconditionnement initial. Les memes taux de reviviscence sont obtenus, soit par immersion directe dans l'eau distillee, soit par exposition a une RH de 100% avant immersion dans l'eau. Aucune difference significative dans la virulence et la capacite a penetrer les larves de Tenebrio molitor n'a ete observee entre les IJ dessechees, apres le preconditionnement pendant 5 jours a une RH de 85% et les IJ n'ayant pas subi ce traitement.
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Plummer, Paul, Orhan Sahin, Eric Burrough, et al. "Critical Role of LuxS in the Virulence of Campylobacter jejuni in a Guinea Pig Model of Abortion." Infection and Immunity 80, no. 2 (2011): 585–93. http://dx.doi.org/10.1128/iai.05766-11.
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ABSTRACTPrevious studies onCampylobacter jejunihave demonstrated the role of LuxS in motility, cytolethal distending toxin production, agglutination, and intestinal colonization; however, its direct involvement in virulence has not been reported. In this study, we demonstrate a direct role ofluxSin the virulence ofC. jejuniin two different animal hosts. The IA3902 strain, a highly virulent sheep abortion strain recently described by our laboratory, along with its isogenicluxSmutant andluxScomplement strains, was inoculated by the oral route into both a pregnant guinea pig virulence model and a chicken colonization model. In both cases, the IA3902luxSmutant demonstrated a complete loss of ability to colonize the intestinal tract. In the pregnant model, the mutant also failed to induce abortion, while the wild-type strain was highly abortifacient. Genetic complementation of theluxSgene fully restored the virulent phenotype in both models. Interestingly, when the organism was inoculated into guinea pigs by the intraperitoneal route, no difference in virulence (abortion induction) was observed between theluxSmutant and the wild-type strain, suggesting that the defect in virulence following oral inoculation is likely associated with a defect in colonization and/or translocation of the organism out of the intestine. These studies provide the first direct evidence that LuxS plays an important role in the virulence ofC. jejuniusing anin vivomodel of natural disease.
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REYES, ANTOLIN L., CLIFFORD H. JOHNSON, PROCTER L. SPAULDING, and GERARD N. STELMA. "Oral Infectivity of Vibrio vulnificus in Suckling Mice." Journal of Food Protection 50, no. 12 (1987): 1013–16. http://dx.doi.org/10.4315/0362-028x-50.12.1013.
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Lethal doses of 11 clinical and environmental isolates of Vibrio vulnificus were determined in suckling mice after oral challenge. With one exception, isolates that were virulent to iron-overloaded adult mice after intraperitoneal inoculation were highly lethal to the infant mice (&gt;50% lethality at 105 CFU/mouse). The virulent isolate that failed to kill infant mice at 105 CFU had lost its invasiveness. Conditionally virulent isolates that were virulent only to simultaneously iron-overloaded and immunosuppressed adult mice required &gt; 109 CFU to kill the infant mice. Avirulent isolates failed to kill at &gt;109 CFU/mouse. There were no significant differences in the lethalities of clinical and environmental isolates. These findings demonstrated a close correlation between virulence in the iron-overloaded adult mouse and infectivity by the oral route.
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Eggenberger, A. L., M. R. Hajimorad, and J. H. Hill. "Gain of Virulence on Rsv1-Genotype Soybean by an Avirulent Soybean mosaic virus Requires Concurrent Mutations in Both P3 and HC-Pro." Molecular Plant-Microbe Interactions® 21, no. 7 (2008): 931–36. http://dx.doi.org/10.1094/mpmi-21-7-0931.
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In soybean, Rsv1, a single dominant resistance gene, invokes extreme resistance (ER) against most Soybean mosaic virus (SMV) strains, including SMV-N, but not SMV-G7, which provokes a virulent lethal systemic hypersensitive response (LSHR). The elicitor functions of the two viruses provoking Rsv1-mediated ER and LSHR have been mapped to the N-terminal 271 amino acids of P3 from SMV-N and SMV-G7, respectively, which differ by nine residues between the two strains. To identify amino acids of P3 from SMV-N provoking Rsv1-mediated ER, the unique residues of SMV-G7 were substituted with those of SMV-N. Of the mutants tested on Rsv1-genotype soybean, only SMV-G7I788R and SMV-G7T948A lost virulence. However, substitution of amino acids of SMV-N, individually or in combination, with the reciprocal residues from SMV-G7 at these two positions failed to confer virulence to SMV-N. In the search for additional virulence determinants, a series of SMV-N chimeras was generated in which fragments within a region from near the middle of the helper-component proteinase (HC-Pro) cistron to the 5′ end of the cytoplasmic inclusion cistron, nucleotides 1,605 to 3,787, were replaced with those of SMV-G7. Only SMV-N-derived chimeras harboring the 3′ region of HC-Pro, at least from nucleotide 2,013, and the entire 5′ end of P3 (nucleotides 2,430 to 3,237) from SMV-G7 were virulent whereas reciprocal exchanges resulted in loss of SMV-G7 virulence. This region of HC-Pro differs by three amino acids between SMV-N and SMV-G7. Analyses of SMV-G7-derived HC-Pro site-directed mutants showed that only SMV-G7M683R lost virulence on Rsv1-genotype soybean; however, SMV-NR682M failed to gain virulence. Nevertheless, an SMV-N derived mutant with three concurrent substitutions, R682M+R787I+A947T, gained virulence. The data indicate that both P3 and HC-Pro are involved in virulence of SMV on Rsv1-genotype soybean.
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Sanz-Ramos, Marta, Fayna Díaz-San Segundo, Cristina Escarmís, Esteban Domingo, and Noemí Sevilla. "Hidden Virulence Determinants in a Viral Quasispecies In Vivo." Journal of Virology 82, no. 21 (2008): 10465–76. http://dx.doi.org/10.1128/jvi.00825-08.
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ABSTRACT The characterization of virulence determinants of pathogenic agents is of utmost relevance for the design of disease control strategies. So far, two classes of virulence determinants have been characterized for viral populations: those imprinted in the nucleotide sequence of some specific genomic regions and those that depend on the complexity of the viral population as such. Here we provide evidence of a virulence determinant that depends neither on a genomic sequence nor on detectable differences in population complexity. Foot-and-mouth disease virus is lethal for C57BL/6 mice showing the highest viral load in pancreas. Virus isolated from pancreas after one passage in mice showed an attenuated phenotype, with no lethality even at the highest dose tested. By contrast, virus from sera of the same mice displayed a virulence similar to that of the parental wild-type clone and virus isolated from spleen displayed an intermediate phenotype. However, viral populations from pancreas, spleen, and serum showed indistinguishable consensus genomic nucleotide sequences and mutant spectrum complexities, as quantified according to the mutation frequencies of both entire genomic nucleotide sequences of biological clones. The results show that the populations with differing virulences cannot be distinguished either by the consensus sequence or by the average complexity of the mutant spectrum. Differential harvesting of virus generated by cell transfection of RNA from serum and pancreas failed to reveal genetic differences between subpopulations endowed with differing virulences. In addition to providing evidence of hidden virulence determinants, this study underlines the capacity of a clone of an RNA virus to rapidly diversify phenotypically in vivo.
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Brandt, Meggin, Kun Yao, Meihong Liu, Robert A. Heckert, and Vikram N. Vakharia. "Molecular Determinants of Virulence, Cell Tropism, and Pathogenic Phenotype of Infectious Bursal Disease Virus." Journal of Virology 75, no. 24 (2001): 11974–82. http://dx.doi.org/10.1128/jvi.75.24.11974-11982.2001.
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ABSTRACT Infectious bursal disease viruses (IBDVs), belonging to the familyBirnaviridae, exhibit a wide range of immunosuppressive potential, pathogenicity, and virulence for chickens. The genomic segment A encodes all the structural (VP2, VP4, and VP3) and nonstructural proteins, whereas segment B encodes the viral RNA-dependent RNA polymerase (VP1). To identify the molecular determinants for the virulence, pathogenic phenotype, and cell tropism of IBDV, we prepared full-length cDNA clones of a virulent strain, Irwin Moulthrop (IM), and constructed several chimeric cDNA clones of segments A and B between the attenuated vaccine strain (D78) and the virulent IM or GLS variant strain. Using the cRNA-based reverse-genetics system developed for IBDV, we generated five chimeric viruses after transfection by electroporation procedures in Vero or chicken embryo fibroblast (CEF) cells, one of which was recovered after propagation in embryonated eggs. To evaluate the characteristics of the recovered viruses in vivo, we inoculated 3-week-old chickens with D78, IM, GLS, or chimeric viruses and analyzed their bursae for pathological lesions 3 days postinfection. Viruses in which VP4, VP4-VP3, and VP1 coding sequences of the virulent strain IM were substituted for the corresponding region in the vaccine strain failed to induce hemorrhagic lesions in the bursa. In contrast, viruses in which the VP2 coding region of the vaccine strain was replaced with the variant GLS or virulent IM strain caused rapid bursal atrophy or hemorrhagic lesions in the bursa, as seen with the variant or classical virulent strain, respectively. These results show that the virulence and pathogenic-phenotype markers of IBDV reside in VP2. Moreover, one of the chimeric viruses containing VP2 sequences of the virulent strain could not be recovered in Vero or CEF cells but was recovered in embryonated eggs, suggesting that VP2 contains the determinants for cell tropism. Similarly, one of the chimeric viruses containing the VP1 segment of the virulent strain could not be recovered in Vero cells but was recovered in CEF cells, suggesting that VP1 contains the determinants for cell-specific replication in Vero cells. By comparing the deduced amino acid sequences of the D78 and IM strains and their reactivities with monoclonal antibody 21, which binds specifically to virulent IBDV, the putative amino acids involved in virulence and cell tropism were identified. Our results indicate that residues Gln at position 253 (Gln253), Asp279, and Ala284 of VP2 are involved in the virulence, cell tropism, and pathogenic phenotype of virulent IBDV.
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Vilei, Edy M., and Joachim Frey. "Genetic and Biochemical Characterization of Glycerol Uptake in Mycoplasma mycoides subsp.mycoides SC: Its Impact on H2O2Production and Virulence." Clinical Diagnostic Laboratory Immunology 8, no. 1 (2001): 85–92. http://dx.doi.org/10.1128/cdli.8.1.85-92.2001.
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ABSTRACT Highly virulent strains of Mycoplasma mycoides subsp.mycoides SC belonging to the African cluster contain an operon with the genes gtsA, gtsB, andgtsC, encoding membrane ATP binding cassette transporter proteins GtsA, GtsB, and GtsC, which are involved in glycerol transport. Strain Afadé from the African cluster incorporated [U-14C]glycerol with a time-dependent increase. The less virulent strain L2 of the European cluster, which lacksgtsB and gtsC, failed to incorporate glycerol. Antibodies against GtsB noncompetitively inhibited glycerol uptake.l-α-Glycerophosphate was not transported by M. mycoides subsp. mycoides SC. It is postulated to be synthesized by phosphorylation of glycerol during transport and subsequently metabolized further to dihydroxyacetone phosphate accompanied by release of H2O2. Peroxide production in glycerol-containing growth medium was high for the African strain Afadé but very low for the European strain L2. Virtually no H2O2 was produced by both strains without glycerol. Hence, the efficient glycerol uptake system found in the virulent strain of the African cluster leads to a strong release of peroxide, a potential virulence factor which is lacking in the less virulent European strains. M. mycoides subsp.mycoides SC might have adopted, as a strategy for virulence, a highly efficient uptake system for glycerol which allows the production of an active metabolic intermediate that damages host cells.
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Setoh, Y. X., N. A. Prow, J. Hobson-Peters, et al. "Identification of residues in West Nile virus pre-membrane protein that influence viral particle secretion and virulence." Journal of General Virology 93, no. 9 (2012): 1965–75. http://dx.doi.org/10.1099/vir.0.044453-0.
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The pre-membrane protein (prM) of West Nile virus (WNV) functions as a chaperone for correct folding of the envelope (E) protein, and prevents premature fusion during virus egress. However, little is known about its role in virulence. To investigate this, we compared the amino acid sequences of prM between a highly virulent North American strain (WNVNY99) and a weakly virulent Australian subtype (WNVKUN). Five amino acid differences occur in WNVNY99 compared with WNVKUN (I22V, H43Y, L72S, S105A and A156V). When expressed in mammalian cells, recombinant WNVNY99 prM retained native antigenic structure, and was partially exported to the cell surface. In contrast, WNVKUN prM (in the absence of the E protein) failed to express a conserved conformational epitope and was mostly retained at the pre-Golgi stage. Substitutions in residues 22 (Ile to Val) and 72 (Leu to Ser) restored the antigenic structure and cell surface expression of WNVKUN prM to the same level as that of WNVNY99, and enhanced the secretion of WNVKUN prME particles when expressed in the presence of E. Introduction of the prM substitutions into a WNVKUN infectious clone (FLSDX) enhanced the secretion of infectious particles in Vero cells, and enhanced virulence in mice. These findings highlight the role of prM in viral particle secretion and virulence, and suggest the involvement of the L72S and I22V substitutions in modulating these activities.
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Allen, Chris A., Paula J. Fedorka-Cray, Andrés Vazquez-Torres, et al. "In Vitro and In Vivo Assessment of Salmonella enterica Serovar Typhimurium DT104 Virulence." Infection and Immunity 69, no. 7 (2001): 4673–77. http://dx.doi.org/10.1128/iai.69.7.4673-4677.2001.
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ABSTRACT Multidrug-resistant Salmonella enterica serovar Typhimurium phage type DT104 has become a widespread cause of human and other animal infection worldwide. The severity of clinical illness inS. enterica serovar Typhimurium DT104 outbreaks has led to the suggestion that this strain possesses enhanced virulence. In the present study, in vitro and in vivo virulence-associated phenotypes of several clinical isolates of S. enterica serovar Typhimurium DT104 were examined and compared to S. entericaserovar Typhimurium ATCC 14028s. The ability of these DT104 isolates to survive within murine peritoneal macrophages, invade cultured epithelial cells, resist antimicrobial actions of reactive oxygen and nitrogen compounds, and cause lethal infection in mice were assessed. Our results failed to demonstrate that S. enterica serovar Typhimurium DT104 isolates are more virulent than S. enterica serovar Typhimurium ATCC 14028s.
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Hajimorad, M. R., A. L. Eggenberger, and J. H. Hill. "Adaptation of Soybean mosaic virus Avirulent Chimeras Containing P3 Sequences from Virulent Strains to Rsv1-Genotype Soybeans Is Mediated by Mutations in HC-Pro." Molecular Plant-Microbe Interactions® 21, no. 7 (2008): 937–46. http://dx.doi.org/10.1094/mpmi-21-7-0937.
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In Rsv1-genotype soybean, Soybean mosaic virus (SMV)-N (an avirulent isolate of strain G2) elicits extreme resistance (ER) whereas strain SMV-G7 provokes a lethal systemic hypersensitive response (LSHR). SMV-G7d, an experimentally evolved variant of SMV-G7, induces systemic mosaic. Thus, for Rsv1-genotype soybean, SMV-N is avirulent whereas SMV-G7 and SMV-G7d are both virulent. Exploiting these differential interactions, we recently mapped the elicitor functions of SMV provoking Rsv1-mediated ER and LSHR to the N-terminal 271 amino acids of P3 from SMV-N and SMV-G7, respectively. The phenotype of both SMV-G7 and SMV-G7d were rendered avirulent on Rsv1-genotype soybean when the part of the genome encoding the N-terminus or the entire P3 cistron was replaced with that from SMV-N; however, reciprocal exchanges did not confer virulence to SMV-N-derived P3 chimeras. Here, we describe virulent SMV-N-derived P3 chimeras containing the full-length or the N-terminal P3 from SMV-G7 or SMV-G7d, with or without additional mutations in P3, that were selected on Rsv1-genotype soybean by sequential transfers on rsv1 and Rsv1-genotype soybean. Sequence analyses of the P3 and helper-component proteinase (HC-Pro) cistrons of progeny recovered from Rsv1-genotype soybean consistently revealed the presence of mutations in HC-Pro. Interestingly, the precise mutations in HC-Pro required for the adaptation varied among the chimeras. No mutation was detected in the HC-Pro of progeny passaged continuously in rsv1-genotype soybean, suggesting that selection is a consequence of pressure imposed by Rsv1. Mutations in HC-Pro alone failed to confer virulence to SMV-N; however, reconstruction of mutations in HC-Pro of the SMV-N-derived P3 chimeras resulted in virulence. Taken together, the data suggest that HC-Pro complementation of P3 is essential for SMV virulence on Rsv1-genotype soybean.
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Suthar, Mehul S., Reed Shabman, Kenya Madric, Cassandra Lambeth, and Mark T. Heise. "Identification of Adult Mouse Neurovirulence Determinants of the Sindbis Virus Strain AR86." Journal of Virology 79, no. 7 (2005): 4219–28. http://dx.doi.org/10.1128/jvi.79.7.4219-4228.2005.
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ABSTRACT Sindbis virus infection of mice has provided valuable insight into viral and host factors that contribute to virus-induced neurologic disease. In an effort to further define the viral genetic elements that contribute to adult mouse neurovirulence, the neurovirulent Sindbis virus strain AR86 was compared to the closely related (22 single amino acid coding changes and the presence or absence of an 18-amino-acid sequence in nsP3 [positions 386 to 403]) but avirulent Girdwood strain. Initial studies using chimeric viruses demonstrated that genetic elements within the nonstructural and structural coding regions contributed to AR86 neurovirulence. Detailed mapping studies identified three major determinants in the nonstructural region, at nsP1 538 (Ile to Thr; avirulent to virulent), an 18-amino-acid deletion in nsP3 (positions 386 to 403), and nsP3 537 (opal to Cys; avirulent to virulent), as well as a single determinant in the structural genes at E2 243 (Leu to Ser; avirulent to virulent), which were essential for AR86 adult mouse neurovirulence. Replacing these codons in AR86 with those found in Girdwood resulted in the attenuation of AR86, while the four corresponding AR86 changes in the Girdwood genetic background increased virulence to the level of wild-type AR86. The attenuating mutations did not adversely affect viral replication in vitro, and the attenuated viruses established infection in the brain and spinal cord as efficiently as the virulent viruses. However, the virus containing the four virulence determinants grew to higher levels in the spinal cord at late times postinfection, suggesting that the virus containing the four attenuating determinants either failed to spread or was cleared more efficiently than the wild-type virus.
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Ramos, Laura S., Brian L. Lehman, Kari A. Peter, and Timothy W. McNellis. "Mutation of theErwinia amylovora argDGene Causes Arginine Auxotrophy, Nonpathogenicity in Apples, and Reduced Virulence in Pears." Applied and Environmental Microbiology 80, no. 21 (2014): 6739–49. http://dx.doi.org/10.1128/aem.02404-14.
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ABSTRACTFire blight is caused byErwinia amylovoraand is the most destructive bacterial disease of apples and pears worldwide. In this study, we found thatE. amylovoraargD(1000)::Tn5, anargDTn5transposon mutant that has the Tn5transposon inserted after nucleotide 999 in theargDgene-coding region, was an arginine auxotroph that did not cause fire blight in apple and had reduced virulence in immature pear fruits. TheE. amylovoraargDgene encodes a predictedN-acetylornithine aminotransferase enzyme, which is involved in the production of the amino acid arginine. A plasmid-borne copy of the wild-typeargDgene complemented both the nonpathogenic and the arginine auxotrophic phenotypes of theargD(1000)::Tn5mutant. However, even when mixed with virulentE. amylovoracells and inoculated onto immature apple fruit, theargD(1000)::Tn5mutant still failed to grow, while the virulent strain grew and caused disease. Furthermore, the pCR2.1-argDcomplementation plasmid was stably maintained in theargD(1000)::Tn5mutant growing in host tissues without any antibiotic selection. Therefore, the pCR2.1-argDcomplementation plasmid could be useful for the expression of genes, markers, and reporters inE. amylovoragrowingin planta, without concern about losing the plasmid over time. The ArgD protein cannot be considered anE. amylovoravirulence factor because theargD(1000)::Tn5mutant was auxotrophic and had a primary metabolism defect. Nevertheless, these results are informative about the parasitic nature of the fire blight disease interaction, since they indicate thatE. amylovoracannot obtain sufficient arginine from apple and pear fruit tissues or from apple vegetative tissues, either at the beginning of the infection process or after the infection has progressed to an advanced state.
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Haralalka, Shruti, Suvobroto Nandi, and Rupak K. Bhadra. "Mutation in the relA Gene of Vibrio cholerae Affects In Vitro and In Vivo Expression of Virulence Factors." Journal of Bacteriology 185, no. 16 (2003): 4672–82. http://dx.doi.org/10.1128/jb.185.16.4672-4682.2003.
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ABSTRACT The relA gene product determines the level of (p)ppGpp, the effector nucleotides of the bacterial stringent response that are also involved in the regulation of other functions, like antibiotic production and quorum sensing. In order to explore the possible involvement of relA in the regulation of virulence of Vibrio cholerae, a relA homolog from the organism (relA VCH) was cloned and sequenced. The relA VCH gene encodes a 738-amino-acid protein having functions similar to those of other gram-negative bacteria, including Escherichia coli. A ΔrelA::kan allele was generated by replacing ∼31% of the open reading frame of wild-type relA of V. cholerae El Tor strain C6709 with a kanamycin resistance gene. The V. cholerae relA mutant strain thus generated, SHK17, failed to accumulate (p)ppGpp upon amino acid deprivation. Interestingly, compared to the wild type, C6709, the mutant strain SHK17 exhibited significantly reduced in vitro production of two principal virulence factors, cholera toxin (CT) and toxin-coregulated pilus (TCP), under virulence gene-inducing conditions. In vivo experiments carried out in rabbit ileal loop and suckling mouse models also confirmed our in vitro results. The data suggest that (p)ppGpp is essential for maximal expression of CT and TCP during in vitro growth, as well as during intestinal infection by virulent V. cholerae. Northern blot and reverse transcriptase PCR analyses indicated significant reduction in the transcript levels of both virulence factors in the relA mutant strain SHK17. Such marked alteration of virulence phenotypes in SHK17 appears most likely to be due to down regulation of transcript levels of toxR and toxT, the two most important virulence regulatory genes of V. cholerae. In SHK17, the altered expression of the two outer membrane porin proteins, OmpU and OmpT, indicated that the relA mutation most likely affects the ToxR-dependent virulence regulatory pathway, because it had been shown earlier that ToxR directly regulates their expression independently of ToxT.
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Brockmeier, Susan L., Crystal L. Loving, Michael A. Mullins, et al. "Virulence, Transmission, and Heterologous Protection of Four Isolates of Haemophilus parasuis." Clinical and Vaccine Immunology 20, no. 9 (2013): 1466–72. http://dx.doi.org/10.1128/cvi.00168-13.
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ABSTRACTHaemophilus parasuiscauses Glässer's disease, a syndrome of polyserositis, meningitis, and arthritis in swine. Previous studies withH. parasuishave revealed virulence disparity among isolates and inconsistent heterologous protection. In this study, virulence, direct transmission, and heterologous protection of 4 isolates ofH. parasuis(SW114, 12939, MN-H, and 29755) were evaluated using a highly susceptible pig model. In an initial experiment, isolates 12939, MN-H, and 29755 caused Glässer's disease, while strain SW114 failed to cause any clinical signs of disease. One pig from each group challenged with MN-H or 29755 failed to develop clinical disease but was able to transmitH. parasuisto noninfected pigs, which subsequently developed Glässer's disease. Pigs colonized with SW114, 29755, or MN-H that were free of clinical disease were protected from a subsequent challenge with isolate 12939. In a following experiment, pigs vaccinated with strain SW114 given as either a bacterin intramuscularly or a live intranasal vaccine were protected from subsequent challenge with isolate 12939; however, some pigs given live SW114 developed arthritis. Overall these studies demonstrated that pigs infected with virulent isolates ofH. parasuiscan remain healthy and serve as reservoirs for transmission to naive pigs and that heterologous protection amongH. parasuisisolates is possible. In addition, further attenuation of strain SW114 is necessary if it is to be used as a live vaccine.
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Lambrechts, Louis, and Thomas W. Scott. "Mode of transmission and the evolution of arbovirus virulence in mosquito vectors." Proceedings of the Royal Society B: Biological Sciences 276, no. 1660 (2009): 1369–78. http://dx.doi.org/10.1098/rspb.2008.1709.
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The traditional assumption that vector-borne pathogens should evolve towards a benign relationship with their arthropod vectors has been challenged on theoretical grounds and empirical evidence. However, in the case of arboviruses (arthropod-borne viruses), although a number of investigators have reported experimental evidence for virus-induced vector mortality, others have failed to detect any significant impact. Whether this variation in the observed level of arbovirus virulence depends on biological traits or experimental design is unclear. Here, we perform a meta-analysis of studies across a range of mosquito–virus systems to show that, overall, arboviruses do reduce the survival of their mosquito vectors, but that the magnitude of the effect depends on the vector/virus taxonomic groups and the mode of virus transmission. Alphaviruses were associated with highest virulence levels in mosquitoes. Horizontal transmission (intrathoracic inoculation or oral infection) was correlated with significant virus-induced mortality, whereas a lack of adverse effect was found for Aedes mosquitoes infected transovarially by bunyaviruses—a group of viruses characterized by high natural rates of vertical transmission in their enzootic vectors. Our findings are consistent with the general prediction that vertically transmitted pathogens should be less virulent than those transmitted horizontally. We conclude that varying degrees of virulence observed among vector–virus systems probably reflect different selective pressures imposed on arboviruses that are primarily transmitted horizontally versus vertically.
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Palmer, Glen E. "Endosomal and AP-3-Dependent Vacuolar Trafficking Routes Make Additive Contributions to Candida albicans Hyphal Growth and Pathogenesis." Eukaryotic Cell 9, no. 11 (2010): 1755–65. http://dx.doi.org/10.1128/ec.00029-10.
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ABSTRACT Candida albicans mutants deficient in vacuolar biogenesis are defective in polarized hyphal growth and virulence. However, the specific vacuolar trafficking routes required for hyphal growth and virulence are unknown. In Saccharomyces cerevisiae, two trafficking routes deliver material from the Golgi apparatus to the vacuole. One occurs via the late endosome and is dependent upon Vps21p, while the second bypasses the endosome and requires the AP-3 complex, including Aps3p. To determine the significance of these pathways in C. albicans hyphal growth and virulence, aps3Δ/Δ, vps21Δ/Δ, and aps3Δ/Δ vps21Δ/Δ mutant strains were constructed. Analysis of vacuolar morphology and localization of the vacuolar protein Mlt1p suggests that C. albicans Aps3p and Vps21p mediate two distinct transport pathways. The vps21Δ/Δ mutant has a minor reduction in hyphal elongation, while the aps3Δ/Δ mutant has no defect in hyphal growth. Interestingly, the aps3Δ/Δ vps21Δ/Δ double mutant has dramatically reduced hyphal growth. Overexpression of the Ume6p transcriptional activator resulted in constitutive hyphal growth of wild-type, aps3Δ/Δ, and vps21Δ/Δ strains and formation of highly vacuolated subapical compartments. Thus, Ume6p-dependent transcriptional responses are sufficient to induce subapical vacuolation. However, the aps3Δ/Δ vps21Δ/Δ mutant formed mainly pseudohyphae that lacked vacuolated compartments. The aps3Δ/Δ strain was virulent in a mouse model of disseminated infection; the vps21Δ/Δ mutant failed to kill mice but persisted within kidney tissue, while the double mutant was avirulent and cleared from the kidneys. These results suggest that while the AP-3 pathway alone has little impact on hyphal growth or virulence, it is much more significant when endosomal trafficking is disrupted.
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Lasco, Todd M., Toshiko Yamamoto, Teizo Yoshimura, Shannon Sedberry Allen, Lynne Cassone, and David N. McMurray. "Effect of Mycobacterium bovis BCG Vaccinationon Mycobacterium-Specific Cellular Proliferation and TumorNecrosis Factor Alpha Production from Distinct Guinea PigLeukocytePopulations." Infection and Immunity 71, no. 12 (2003): 7035–42. http://dx.doi.org/10.1128/iai.71.12.7035-7042.2003.
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ABSTRACT In this study, we focused on three leukocyte-rich guinea pig cell populations, bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live attenuated Mycobacterium tuberculosis H37Ra or with live or heat-killed virulent M. tuberculosis H37Rv (multiplicity of infection of 1:100). Each cell population was determined to proliferate in response to heat-killed virulent H37Rv, whereas no measurable proliferative response could be detected upon stimulation with live mycobacteria. Additionally, this proliferative capacity (in SPC and PC populations) was significantly enhanced upon prior vaccination with Mycobacterium bovis BCG. Accordingly, in a parallel set of experiments we found a strong positive correlation between production of antigen-specific bioactive tumor necrosis factor alpha (TNF-α) and prior vaccination with BCG. A nonspecific stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and PC. These results showed that production of bioactive TNF-α from mycobacterium-stimulated guinea pig cell cultures positively correlates with the vaccination status of the host and with the virulence of the mycobacterial strain.
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Vijayakumar, Karuppiah, Vajravelu Manigandan, Danaraj Jeyapragash, Veeraiyan Bharathidasan, Balaiyan Anandharaj, and Madhavan Sathya. "Eucalyptol inhibits biofilm formation of Streptococcus pyogenes and its mediated virulence factors." Journal of Medical Microbiology 69, no. 11 (2020): 1308–18. http://dx.doi.org/10.1099/jmm.0.001253.
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Introduction. Streptococcus pyogenes is a diverse virulent synthesis pathogen responsible for invasive systemic infections. Establishment of antibiotic resistance in the pathogen has produced a need for new antibiofilm agents to control the biofilm formation and reduce biofilm-associated resistance development. Aim. The present study investigates the in vitro antibiofilm activity of eucalyptol against S. pyogenes . Methodology. The antibiofilm potential of eucalyptol was assessed using a microdilution method and their biofilm inhibition efficacy was visualized by microscopic analysis. The biochemical assays were performed to assess the influence of eucalyptol on virulence productions. Real-time PCR analysis was performed to evaluate the expression profile of the virulence genes. Results. Eucalyptol showed significant antibiofilm potential in a dose-dependent manner without affecting bacterial growth. Eucalyptol at 300 µg ml−1 (biofilm inhibitory concentration) significantly inhibited the initial stage of biofilm formation in S. pyogenes . However, eucalyptol failed to diminish the mature biofilms of S. pyogenes at biofilm inhibitory concentration and it effectively reduced the biofilm formation on stainless steel, titanium, and silicone surfaces. The biochemical assay results revealed that eucalyptol greatly affects the cell-surface hydrophobicity, auto-aggregation, extracellular protease, haemolysis and hyaluronic acid synthesis. Further, the gene-expression analysis results showed significant downregulation of virulence gene expression upon eucalyptol treatment. Conclusion. The present study suggests that eucalyptol applies its antibiofilm assets by intruding the initial biofilm formation of S. pyogenes . Supplementary studies are needed to understand the mode of action involved in biofilm inhibition.
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Le Monnier, Alban, Nicolas Autret, Olivier F. Join-Lambert, et al. "ActA Is Required for Crossing of the Fetoplacental Barrier by Listeria monocytogenes." Infection and Immunity 75, no. 2 (2006): 950–57. http://dx.doi.org/10.1128/iai.01570-06.
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ABSTRACT The facultative intracellular bacterial pathogen Listeria monocytogenes induces severe fetal infection during pregnancy. Little is known about the molecular mechanisms allowing the maternofetal transmission of bacteria. In this work, we studied fetoplacental invasion by infecting mice with various mutants lacking virulence factors involved in the intracellular life cycle of L. monocytogenes. We found that the placenta was highly susceptible to bacteria, including avirulent bacteria, such as an L. monocytogenes mutant with an hly deletion (ΔLLO) and a nonpathogenic species, Listeria innocua, suggesting that permissive trophoblastic cells, trapping bacteria, provide a protective niche for bacterial survival. The ΔLLO mutant, which is unable to escape the phagosomal compartment of infected cells, failed to grow in the trophoblast tissue and to invade the fetus. Mutant bacteria with inlA and inlB deletion (ΔInlAB) grew in the placenta and fetus as well as did the wild-type virulent stain (EGDwt), indicating that in the murine model, internalins A and B are not involved in fetoplacental invasion by L. monocytogenes. Pregnant mice were then infected with an actA deletion (ΔActA) strain, a virulence-attenuated mutant that is unable to polymerize actin and to spread from cell to cell. With the ΔActA mutant, fetal infection occurs, but with a significant delay and restriction, and it requires a placental bacterial load 2 log units higher than that for the wild-type virulent strain. Definitive evidence for the role of ActA was provided by showing that a actA-complemented ΔActA mutant was restored in its capacity to invade fetuses. ActA-mediated cell-to-cell spreading plays a major role in the vertical transmission of L. monocytogenes to the fetus in the murine model.
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Shen, Wei-Chiang, Robert C. Davidson, Gary M. Cox, and Joseph Heitman. "Pheromones Stimulate Mating and Differentiation via Paracrine and Autocrine Signaling in Cryptococcus neoformans." Eukaryotic Cell 1, no. 3 (2002): 366–77. http://dx.doi.org/10.1128/ec.1.3.366-377.2002.
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ABSTRACT Cryptococcus neoformans is a pathogenic fungus with a defined sexual cycle involving haploid MATα and MATa cells. Interestingly, MATα strains are more common, are more virulent than congenic MATa strains, and undergo haploid fruiting in response to nitrogen limitation or MATa cells. Three genes encoding the MFα pheromone were identified in the MATα mating-type locus and shown to be transcriptionally induced by limiting nutrients and coculture with MATa cells. The MFα1, MFα2, and MFα3 genes were mutated, individually and in combination. MATα strains lacking MFα pheromone failed to induce morphological changes in MATa cells. Pheromoneless MATα mutants were fusion and mating impaired but not sterile and mated at ∼1% the wild-type level. The pheromoneless MATα mutants were also partially defective in haploid fruiting, and overexpression of MFα pheromone enhanced haploid fruiting. Overexpression of MFa pheromone also enhanced haploid fruiting of MATα cells and stimulated conjugation tube formation in MATa cells. A conserved G-protein activated mitogen-activated protein kinase signaling pathway was found to be required for both induction and response to mating pheromones. The MFα pheromone was not essential for virulence of C. neoformans but does contribute to the overall virulence composite. These studies define paracrine and autocrine pheromone response pathways that signal mating and differentiation of this pathogenic fungus.
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Gellatly, Shaan L., Brittany Needham, Laurence Madera, M. Stephen Trent, and Robert E. W. Hancock. "The Pseudomonas aeruginosa PhoP-PhoQ Two-Component Regulatory System Is Induced upon Interaction with Epithelial Cells and Controls Cytotoxicity and Inflammation." Infection and Immunity 80, no. 9 (2012): 3122–31. http://dx.doi.org/10.1128/iai.00382-12.
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ABSTRACTThe adaptation ofPseudomonas aeruginosato its environment, including the host, is tightly controlled by its network of regulatory systems. The two-component regulatory system PhoPQ has been shown to play a role in the virulence and polymyxin resistance ofP. aeruginosaas well as several other Gram-negative species. Dysregulation of this system has been demonstrated in clinical isolates, yet how it affects virulence ofP. aeruginosais unknown. To investigate this, an assay was used whereby bacteria were cocultured with human bronchial epithelial cells. The interaction of wild-type (WT) bacteria that had adhered to epithelial cells led to a large upregulation of the expression of theoprH-phoP-phoQoperon and its target, thearnlipopolysaccharide (LPS) modification operon, in a PhoQ-dependent manner, compared to cells in the supernatant that had failed to adhere. Relative to the wild type, aphoQmutant cocultured on epithelial cells produced less secreted protease and lipase and, like thephoQmutant,piv,lipH, andlasBmutants demonstrated reduced cytotoxicity toward epithelial cells. Mutation inphoQalso resulted in alterations to lipid A and to increased inflammatory LPS. These data indicate that mutation ofphoQresults in a phenotype that is similar to the less virulent but more inflammatory phenotype of clinical strains isolated from chronic-stage cystic fibrosis lung infections.
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North, R. J., and A. A. Izzo. "Mycobacterial virulence. Virulent strains of Mycobacteria tuberculosis have faster in vivo doubling times and are better equipped to resist growth-inhibiting functions of macrophages in the presence and absence of specific immunity." Journal of Experimental Medicine 177, no. 6 (1993): 1723–33. http://dx.doi.org/10.1084/jem.177.6.1723.
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The kinetics of growth of two virulent strains of mycobacteria (M. tuberculosis Erdman and M. tuberculosis H37Rv) and two attenuated strains (M. tuberculosis H37Ra and M. bovis Bacillus Calmette-Guerin [BCG]) were studied in the lungs, livers, spleens, and kidneys of severe combined immunodeficient (SCID) mice and of their coisogenic CB-17 immunocompetent counterparts. It was found, in keeping with the findings of earlier investigators (Pierce, C. H., R. J. Dubos, and W. B. Schaefer. 1953. J. Exp. Med. 97:189.), that in immunocompetent mice, virulent organisms grew progressively only in the lungs, whereas the growth of attenuated organisms was controlled in all organs. In SCID mice, in contrast, virulent mycobacteria grew rapidly and progressively in all organs, as did BCG, although at a slower rate. However, H37Ra failed to grow progressively in any organs of SCID mice, unless the mice were treated with hydrocortisone. In fact, hydrocortisone treatment enabled virulent, as well as attenuated, organisms to grow strikingly more rapidly in all organs of SCID mice and in all organs of CB-17 mice. A histological study showed that in SCID mice, multiplication of mycobacteria in the liver occurs in the cytoplasm of macrophages in granulomas and presumably in macrophages in other organs. It is suggested, therefore, that the macrophages of SCID mice possess a glucocorticoid-sensitive mycobacterial mechanism that prevents virulent and avirulent mycobacteria from expressing their true minimal doubling times. In the absence of this mechanism in the lungs of hydrocortisone-treated SCID mice, the doubling times of Erdman, H37Rv, BCG, and H37Ra were 17.7, 17.4, 44.6, and 98.6 h, respectively. The possible importance of a rapid multiplication rate for mycobacterial virulence is discussed.
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Bouloy, Michèle, Christian Janzen, Pierre Vialat, et al. "Genetic Evidence for an Interferon-Antagonistic Function of Rift Valley Fever Virus Nonstructural Protein NSs." Journal of Virology 75, no. 3 (2001): 1371–77. http://dx.doi.org/10.1128/jvi.75.3.1371-1377.2001.
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ABSTRACT Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR−/− mice lacking the alpha/beta interferon (IFN-α/β) receptor but remained attenuated in IFN-γ receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-α/β production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-α/β and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-α/β production, we infected susceptible IFNAR−/− mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-α/β production. These results demonstrate that the ability of RVFV to inhibit IFN-α/β production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist.
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Qin, Aiping, David W. Scott, Jennifer A. Thompson, and Barbara J. Mann. "Identification of an Essential Francisella tularensis subsp. tularensis Virulence Factor." Infection and Immunity 77, no. 1 (2008): 152–61. http://dx.doi.org/10.1128/iai.01113-08.
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ABSTRACT Francisella tularensis, the highly virulent etiologic agent of tularemia, is a low-dose intracellular pathogen that is able to escape from the phagosome and replicate in the cytosol. Although there has been progress in identifying loci involved in the pathogenicity of this organism, analysis of the genome sequence has revealed few obvious virulence factors. We previously reported isolation of an F. tularensis subsp. tularensis strain Schu S4 transposon insertion mutant with a mutation in a predicted hypothetical lipoprotein, FTT1103, that was deficient in intracellular replication in HepG2 cells. In this study, a mutant with a defined nonpolar deletion in FTT1103 was created, and its phenotype, virulence, and vaccine potential were characterized. A phagosomal integrity assay and lysosome-associated membrane protein 1 colocalization revealed that ΔFTT1103 mutant bacteria were defective in phagosomal escape. FTT1103 mutant bacteria were maximally attenuated in the mouse model; mice survived, without visible signs of illness, challenge by more than 1010 CFU when the intranasal route was used and challenge by 106 CFU when the intraperitoneal, subcutaneous, or intravenous route was used. The FTT1103 mutant bacteria exhibited dissemination defects. Mice that were infected by the intranasal route had low levels of bacteria in their livers and spleens, and these bacteria were cleared by 3 days postinfection. Mutant bacteria inoculated by the subcutaneous route failed to disseminate to the lungs. BALB/c or C57BL/6 mice that were intranasally vaccinated with 108 CFU of FTT1103 mutant bacteria were protected against subsequent challenge with wild-type strain Schu S4. These experiments identified the FTT1103 protein as an essential virulence factor and also demonstrated the feasibility of creating defined attenuated vaccines based on a type A strain.
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Sze, Ching Wooen, Kai Zhang, Toru Kariu, Utpal Pal, and Chunhao Li. "Borrelia burgdorferi Needs Chemotaxis To Establish Infection in Mammals and To Accomplish Its Enzootic Cycle." Infection and Immunity 80, no. 7 (2012): 2485–92. http://dx.doi.org/10.1128/iai.00145-12.
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ABSTRACTBorrelia burgdorferi, the causative agent of Lyme disease, can be recovered from different organs of infected animals and patients, indicating that the spirochete is very invasive. Motility and chemotaxis contribute to the invasiveness ofB. burgdorferiand play important roles in the process of the disease. Recent reports have shown that motility is required for establishing infection in mammals. However, the role of chemotaxis in virulence remains elusive. Our previous studies showed thatcheA2, a gene encoding a histidine kinase, is essential for the chemotaxis ofB. burgdorferi. In this report, thecheA2gene was inactivated in a low-passage-number virulent strain ofB. burgdorferi. In vitroanalyses (microscopic observations, computer-based bacterial tracking analysis, swarm plate assays, and capillary tube assays) showed that thecheA2mutant failed to reverse and constantly ran in one direction; the mutant was nonchemotactic to attractants. Mouse needle infection studies showed that thecheA2mutant failed to infect either immunocompetent or immunodeficient mice and was quickly eliminated from the initial inoculation sites. Tick-mouse infection studies revealed that although the mutant was able to survive in ticks, it failed to establish a new infection in mice via tick bites. The altered phenotypes were completely restored when the mutant was complemented. Collectively, these data demonstrate thatB. burgdorferineeds chemotaxis to establish mammalian infection and to accomplish its natural enzootic cycle.
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Robertson, Gregory T., Wai-Leung Ng, Joseph Foley, Raymond Gilmour, and Malcolm E. Winkler. "Global Transcriptional Analysis of clpP Mutations of Type 2 Streptococcus pneumoniae and Their Effects on Physiology and Virulence." Journal of Bacteriology 184, no. 13 (2002): 3508–20. http://dx.doi.org/10.1128/jb.184.13.3508-3520.2002.
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ABSTRACT Streptococcus pneumoniae is an important human pathogen that contains single copies of genes encoding the ClpP and FtsH ATP-dependent proteases but lacks the Lon and HslV proteases. We constructed and characterized the phenotypes of clpP, clpC, and clpX deletion replacement mutants, which lack the ClpP protease subunit or the putative ClpC or ClpX ATPase specificity factor. A ΔclpP mutant, but not a ΔclpC or ΔclpX mutant, of the virulent D39 type 2 strain of S. pneumoniae grew poorly at 30°C and failed to grow at 40°C. Despite this temperature sensitivity, transcription of the heat shock regulon determined by microarray analysis was induced in a ΔclpP mutant, which was also more sensitive to oxidative stress by H2O2 and to puromycin than its clpP + parent strain. A ΔclpP mutant, but not a ΔclpC mutant, was strongly attenuated for virulence in the murine lung and sepsis infection models. All of these phenotypes were complemented in a ΔclpP/clpP + merodiploid strain. Consistent with these complementation patterns, clpP was found to be in a monocistronic operon, whose transcription was induced about fivefold by heat shock in S. pneumoniae as determined by Northern and real-time reverse transcription-PCR analyses. Besides clpP, transcription of clpC, clpE, and clpL, but not clpX or ftsH, was induced by heat shock or entry into late exponential growth phase. Microarray analysis of ΔclpP mutants showed a limited change in transcription pattern (≈80 genes) consistent with these phenotypes, including repression of genes involved in oxidative stress, metal ion transport, and virulence. In addition, transcription of the early and late competence regulon was induced in the ΔclpP mutant, and competence gene expression and DNA uptake seemed to be constitutively induced throughout growth. Together, these results indicate that ClpP-mediated proteolysis plays a complex and central role in numerous pneumococcal stress responses, development of competence, and virulence.
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Ramírez, Melissa A., and Michael C. Lorenz. "Mutations in Alternative Carbon Utilization Pathways in Candida albicans Attenuate Virulence and Confer Pleiotropic Phenotypes." Eukaryotic Cell 6, no. 2 (2006): 280–90. http://dx.doi.org/10.1128/ec.00372-06.
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ABSTRACT The interaction between Candida albicans and cells of the innate immune system is a key determinant of disease progression. Transcriptional profiling has revealed that C. albicans has a complex response to phagocytosis, much of which is similar to carbon starvation. This suggests that nutrient limitation is a significant stress in vivo, and we have shown that glyoxylate cycle mutants are less virulent in mice. To examine whether other aspects of carbon metabolism are important in vivo during an infection, we have constructed strains lacking FOX2 and FBP1, which encode key components of fatty acid β-oxidation and gluconeogenesis, respectively. As expected, fox2Δ mutants failed to utilize several fatty acids as carbon sources. Surprisingly, however, these mutants also failed to grow in the presence of several other carbon sources, whose assimilation is independent of β-oxidation, including ethanol and citric acid. Mutants lacking the glyoxylate enzyme ICL1 also had more severe carbon utilization phenotypes than were expected. These results suggest that the regulation of alternative carbon metabolism in C. albicans is significantly different from that in other fungi. In vivo, fox2Δ mutants show a moderate but significant reduction in virulence in a mouse model of disseminated candidiasis, while disruption of the glyoxylate cycle or gluconeogenesis confers a severe attenuation in this model. These data indicate that C. albicans often encounters carbon-poor conditions during growth in the host and that the ability to efficiently utilize multiple nonfermentable carbon sources is a virulence determinant. Consistent with this in vivo requirement, C. albicans uniquely regulates carbon metabolism in a more integrated manner than in Saccharomyces cerevisiae, such that defects in one part of the machinery have wider impacts than expected. These aspects of alternative carbon metabolism may then be useful as targets for therapeutic intervention.
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Eizenberg, H., D. Plakhine, T. Landa, G. Achdari, D. M. Joel, and J. Hershenhorn. "First Report of a New Race of Sunflower Broomrape (Orobanche cumana) in Israel." Plant Disease 88, no. 11 (2004): 1284. http://dx.doi.org/10.1094/pdis.2004.88.11.1284c.
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The genus Orobanche includes chlorophyll-lacking root parasites that parasitize many dicotyledonous species and causes severe damage to vegetable and field crops worldwide. Sunflower broomrape (Orobanche cumana Wallr.) is known in Eurasia as a specific parasite of sunflower, which differs from the nodding broomrape (O. cernua Loefl) in host specificity and morphological characteristics (3). Together with Egyptian broomrape (O. aegyptiaca Pers.), it seriously parasitizes sunflower (Helianthus annuus L.) in Israel (1). Prior to 2000, the local confectionary sunflower cvs. Ambar and Gitit proved to be resistant to the local O. cumana populations in Israel (2). A preliminary study, which we conducted in 1995 using the Vranceanu's differentials (4), indicated that O. cumana populations in Israel behave like the known race C. Using random amplified polymorphic DNA analysis, we also found a very low intraspecific diversity of this species in Israel at that time. However, in 2000, infection of the sunflower cvs. Ambar and Gitit was reported in two fields (Gadot and Afek) in northern Israel. In 2001 and 2002, O. cumana parasitized these cultivars in three more locations as much as 50 km apart (Tel-Adashim, Mevo-Hama, and Bet-Hilel). To determine the virulence of O. cumana populations on sunflower cultivars under controlled conditions, O. cumana seeds were collected in the above mentioned sunflower fields. In addition, we also used seeds from an O. cumana population collected in Alonim in 1997. This latter population did not infect the above mentioned ‘resistant’ sunflower cultivars in the field (2,); therefore, represented the previously known O. cumana populations in Israel. Resistant (Ambar) and susceptible (D.Y.3) sunflower cultivars were planted in separate pots that were differentially filled with soil that was inoculated with O. cumana seeds of the different populations. The experiment was performed in a full factorial arrangement with six replications. As expected, O. cumana from Alonim failed to attack the resistant sunflower. However, the O. cumana populations that were collected in the five other fields seriously attacked both sunflower cultivars, indicating higher virulence. O. cumana from all five new populations proved more virulent than the Alonim population on cvs. Ambar and D.Y.3. The occurrence of these new virulent populations could have several reasons including: (i) importation of virulent parasite seeds from abroad; or (ii) local development of virulence from previously avirulent populations. The latter could be favored by the continuous and repeated use of the available resistant varieties that are all based on a single resistance response (2). References: (1) H. Eizenberg and D. M. Joel. Orobanche in Israeli agriculture. Workshop of COST Action 849, Parasitic Plant Management in Sustainable Agriculture, 2001. (2) H. Eizenberg et al. Plant Dis. 88:479, 2003. (3) D. M. Joel. Phytoparasitica 16:375, 1988. (4) A. V. Vranceanu et al. Proc. 9th Sunflower Conf. 1:74–82, 1980.
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Vega, Byron, and Megan M. Dewdney. "QoI-Resistance Stability in Relation to Pathogenic and Saprophytic Fitness Components of Alternaria alternata from Citrus." Plant Disease 98, no. 10 (2014): 1371–78. http://dx.doi.org/10.1094/pdis-01-14-0078-re.
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The phenotypic stability, fitness components, and ability to cause disease of isolates of the Alternaria alternata tangerine pathotype resistant to quinone-outside inhibitors (QoIs) were studied. Stability of resistance to azoxystrobin (AZ) and pyraclostrobin (PYR) was determined after consecutive transfers on potato dextrose agar (PDA). The sensitivity to QoIs did not change significantly after 10 transfers on PDA compared with the initial sensitivity of all isolates tested. Fitness components evaluated in vitro were mycelial growth, conidial germination, and conidial production. Incubation period, number of lesions per leaf area, and virulence were determined with detached leaf assays using four cultivars: Dancy, Minneola, Murcott, and Sunburst. Variability in fitness components was observed among isolates within the same sensitivity group. As a group, no significant differences in the mean values of these fitness components were observed between resistant and sensitive phenotypes, except for virulence. Resistant isolates were significantly (P < 0.05) more virulent than the sensitive isolates on Dancy, Minneola, and Sunburst but not on Murcott (P = 0.3506). There was no significant correlation between individual fitness components and the level of sensitivity to AZ and PYR. Preventive applications of Abound (commercial formulation of AZ) at full field rates failed to control disease caused by QoI-resistant isolates under greenhouse conditions. Our results suggest that QoI resistance in A. alternata tangerine pathotype is stable in the absence of QoI selection pressure and that resistance development did not affect the fitness of resistant isolates.
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Rohrlack, Thomas, Guntram Christiansen, and Rainer Kurmayer. "Putative Antiparasite Defensive System Involving Ribosomal and Nonribosomal Oligopeptides in Cyanobacteria of the Genus Planktothrix." Applied and Environmental Microbiology 79, no. 8 (2013): 2642–47. http://dx.doi.org/10.1128/aem.03499-12.
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ABSTRACTParasitic chytrid fungi can inflict significant mortality on cyanobacteria but frequently fail to keep cyanobacterial dominance and bloom formation in check. Our study tested whether oligopeptide production, a common feature in many cyanobacteria, can be a defensive mechanism against chytrid parasitism. The study employed the cyanobacterial strainPlanktothrixNIVA-CYA126/8 and its mutants with knockout mutations for microcystins, anabaenopeptins, and microviridins, major oligopeptide classes to be found in NIVA-CYA126/8. Four chytrid strains were used as parasite models. They are obligate parasites ofPlanktothrixand are unable to exploit alternative food sources. All chytrid strains were less virulent to the NIVA-CYA126/8 wild type than to at least one of its oligopeptide knockout mutants. One chytrid strain even failed to infect the wild type, while exhibiting considerable virulence to all mutants. It is therefore evident that producing microcystins, microviridins, and/or anabaenopeptins can reduce the virulence of chytrids toPlanktothrix, thereby increasing the host's chance of survival. Microcystins and anabaenopeptins are nonribosomal oligopeptides, while microviridins are produced ribosomally, suggesting thatPlanktothrixresists chytrids by relying on metabolites that are produced via distinct biosynthetic pathways. Chytrids, on the other hand, can adapt to the oligopeptides produced byPlanktothrixin different ways. This setting most likely results in an evolutionary arms race, which would probably lead toPlanktothrixand chytrid population structures that closely resemble those actually found in nature. In summary, the findings of the present study suggest oligopeptide production inPlanktothrixto be part of a defensive mechanism against chytrid parasitism.
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Pechous, Roger, Jean Celli, Renee Penoske, Stanley F. Hayes, Dara W. Frank, and Thomas C. Zahrt. "Construction and Characterization of an Attenuated Purine Auxotroph in a Francisella tularensis Live Vaccine Strain." Infection and Immunity 74, no. 8 (2006): 4452–61. http://dx.doi.org/10.1128/iai.00666-06.
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ABSTRACT Francisella tularensis is a facultative intracellular pathogen and is the etiological agent of tularemia. It is capable of escaping from the phagosome, replicating to high numbers in the cytosol, and inducing apoptosis in macrophages of a variety of hosts. F. tularensis has received significant attention recently due to its potential use as a bioweapon. Currently, there is no licensed vaccine against F. tularensis, although a partially protective live vaccine strain (LVS) that is attenuated in humans but remains fully virulent for mice was previously developed. An F. tularensis LVS mutant deleted in the purMCD purine biosynthetic locus was constructed and partially characterized by using an allelic exchange strategy. The F. tularensis LVS ΔpurMCD mutant was auxotrophic for purines when grown in defined medium and exhibited significant attenuation in virulence when assayed in murine macrophages in vitro or in BALB/c mice. Growth and virulence defects were complemented by the addition of the purine precursor hypoxanthine or by introduction of purMCDN in trans. The F. tularensis LVS ΔpurMCD mutant escaped from the phagosome but failed to replicate in the cytosol or induce apoptotic and cytopathic responses in infected cells. Importantly, mice vaccinated with a low dose of the F. tularensis LVSΔ purMCD mutant were fully protected against subsequent lethal challenge with the LVS parental strain. Collectively, these results suggest that F. tularensis mutants deleted in the purMCD biosynthetic locus exhibit characteristics that may warrant further investigation of their use as potential live vaccine candidates.
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Riendeau, Carrie J., and Hardy Kornfeld. "THP-1 Cell Apoptosis in Response to Mycobacterial Infection." Infection and Immunity 71, no. 1 (2003): 254–59. http://dx.doi.org/10.1128/iai.71.1.254-259.2003.
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ABSTRACT We previously reported that Mycobacterium tuberculosis infection primes human alveolar macrophages (HAM) for tumor necrosis factor alpha (TNF-α)-mediated apoptosis and that macrophage apoptosis is associated with killing internalized bacilli. Virulent mycobacterial strains elicit much less apoptosis than attenuated strains, implying that apoptosis is a defense against intracellular infection. The present study evaluated the potential for phorbol myristate acetate-differentiated THP-1 cells to mimic this response of primary macrophages. Consistent with the behavior of alveolar macrophages, attenuated M. tuberculosis H37Ra and Mycobacterium bovis BCG strongly induce THP-1 apoptosis, which requires endogenous TNF. THP-1 apoptosis is associated with reduced viability of infecting BCG. In contrast, virulent wild-type M. tuberculosis H37Rv and M. bovis do not increase THP-1 apoptosis over baseline. BCG induced early activation of caspase 10 and 9, followed by caspase 3. In contrast, wild-type M. bovis infection failed to activate any caspases in THP-1 cells. BCG-induced THP-1 apoptosis is blocked by retroviral transduction with vectors expressing crmA but not bcl-2. We conclude that differentiated THP-1 cells faithfully model the apoptosis response of HAM. Analysis of the THP-1 cell response to infection with virulent mycobacteria suggests that TNF death signals are blocked proximal to initiator caspase activation, at the level of TNF receptor 1 or its associated intracytoplasmic adaptor complex. Interference with TNF death signaling may be a virulence mechanism that allows M. tuberculosis to circumvent innate defenses leading to apoptosis of infected host cells.
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Wilson, Duncan, François L. Mayer, Pedro Miramón, et al. "Distinct Roles of Candida albicans-Specific Genes in Host-Pathogen Interactions." Eukaryotic Cell 13, no. 8 (2014): 977–89. http://dx.doi.org/10.1128/ec.00051-14.
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ABSTRACTHuman fungal pathogens are distributed throughout their kingdom, suggesting that pathogenic potential evolved independently.Candida albicansis the most virulent member of the CUG clade of yeasts and a common cause of both superficial and invasive infections. We therefore hypothesized thatC. albicanspossesses distinct pathogenicity mechanisms.In silicogenome subtraction and comparative transcriptional analysis identified a total of 65C.albicans-specificgenes (ASGs) expressed during infection. Phenotypic characterization of six ASG-null mutants demonstrated that these genes are dispensable forin vitrogrowth but play defined roles in host-pathogen interactions. Based on these analyses, we investigated two ASGs in greater detail. An orf19.6688Δ mutant was found to be fully virulent in a mouse model of disseminated candidiasis and to induce higher levels of the proinflammatory cytokine interleukin-1β (IL-1β) following incubation with murine macrophages. Apga16Δ mutant, on the other hand, exhibited attenuated virulence. Moreover, we provide evidence that secondary filamentation events (multiple hyphae emerging from a mother cell and hyphal branching) contribute to pathogenicity:PGA16deletion did not influence primary hypha formation or extension following contact with epithelial cells; however, multiple hyphae and hyphal branching were strongly reduced. Significantly, these hyphae failed to damage host cells as effectively as the multiple hypha structures formed by wild-typeC. albicanscells. Together, our data show that species-specific genes of a eukaryotic pathogen can play important roles in pathogenicity.
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Lee, Mi Yeon, Lijie Yan, Florien A. Gorter, et al. "Brachypodium distachyon line Bd3-1 resistance is elicited by the barley stripe mosaic virus triple gene block 1 movement protein." Journal of General Virology 93, no. 12 (2012): 2729–39. http://dx.doi.org/10.1099/vir.0.045880-0.
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Barley stripe mosaic virus North Dakota 18 (ND18), Beijing (BJ), Xinjiang (XJ), Type (TY) and CV21 strains are unable to infect the Brachypodium distachyon Bd3-1 inbred line, which harbours a resistance gene designated Bsr1, but the Norwich (NW) strain is virulent on Bd3-1. Analysis of ND18 and NW genomic RNA reassortants and RNAβ mutants demonstrates that two amino acids within the helicase motif of the triple gene block 1 (TGB1) movement protein have major effects on their Bd3-1 phenotypes. Resistance to ND18 correlates with an arginine residue at TGB1 position 390 (R390) and a threonine at position 392 (T392), whereas the virulent NW strain contains lysines (K) at both positions. ND18 TGB1 R390K (NDTGB1R390K) and NDTGB1T392K single substitutions, and an NDTGB1R390K,T392K double mutation resulted in systemic infections of Bd3-1. Reciprocal NDTGB1 substitutions into NWTGB1 (NWTGB1K390R and NWTGB1K392T) failed to affect virulence, implying that K390 and K392 compensate for each other. In contrast, an NWTGB1K390R,K392T double mutant exhibited limited vascular movement in Bd3-1, but developed prominent necrotic streaks that spread from secondary leaf veins. This phenotype, combined with the appearance of necrotic spots in certain ND18 mutants, and necrosis and rapid wilting of Bd3-1 plants after BJ strain (BJTGB1K390,T392) inoculations, show that Bd3-1 Bsr1 resistance is elicited by the TGB1 protein and suggest that it involves a hypersensitive response.
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Denise, Hubert, Kathryn McNeil, Darren R. Brooks, James Alexander, Graham H. Coombs, and Jeremy C. Mottram. "Expression of Multiple CPB Genes Encoding Cysteine Proteases Is Required for Leishmania mexicana Virulence In Vivo." Infection and Immunity 71, no. 6 (2003): 3190–95. http://dx.doi.org/10.1128/iai.71.6.3190-3195.2003.
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ABSTRACT Leishmania mexicana mutants deficient in the multicopy CPB gene array have reduced virulence, demonstrated by poor lesion growth in BALB/c mice and induction of a protective Th1 response. Reinsertion of the amastigote-specific CPB2.8 or metacyclic stage-specific CPB2 gene into a CPB-deficient mutant L. mexicana failed to restore either a Th2 response or sustained virulence. However, reexpression of multiple CPB genes from a cosmid significantly restored virulence. This was characterized by increased lesion and parasite growth and the acquisition of a Th2 response, as determined by measuring interleukin-4 production and immunoglobulin G1 (IgG1) and IgE levels. These studies confirm that L. mexicana cysteine proteases are important virulence factors and provide an explanation for the presence in L. mexicana of a multicopy tandem array of CPB genes.
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Cole, Barry C., Hong-Hua Mu, Nathan D. Pennock, et al. "Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components from Mycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2." Infection and Immunity 73, no. 9 (2005): 6039–47. http://dx.doi.org/10.1128/iai.73.9.6039-6047.2005.
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ABSTRACT Mycoplasma arthritidis induces toxicity, arthritis, and dermal necrosis in mice. Virulence factors include a superantigen and membrane adhesins and possibly also a bacteriophage component. Here we compare the biological properties of Triton X-114 extracts derived from avirulent and virulent M. arthritidis strains. Macrophage cell lines and resident peritoneal macrophages were used to assess inflammatory potential as indicated by production of tumor necrosis factor alpha, interleukin-6, and/or nitric oxide. The activity resided exclusively within the hydrophobic detergent phase, was unaffected by heat treatment at 100°C for 30 min, and was resistant to proteinase K digestion, suggesting involvement of a lipopeptide. Contamination of extracts with endotoxin or superantigen was excluded. Extracts of the more virulent strain had higher activity than did those of the avirulent strain. Using CHO cells expressing Toll-like receptor 2 (TLR2) or TLR4, both with transfected CD14, we showed that extracts activated these cells via TLR2 but not by TLR4. Also, macrophages from C57BL/6 TLR2−/− mice failed to respond to the extracts, whereas those from TLR2+/+ cells did respond. The preparations from the virulent strain of M. arthritidis were also more potent in activating dendritic cells, as evidenced by up-regulation of major histocompatibility complex class II, CD40, B7-1, and B7-2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent elution of gel slices revealed the presence of three active moieties which corresponded to molecular masses of approximately 24, 28, and 40 kDa. Three active components were also found by reverse-phase chromatography. We suggest that macrophage activation by M. arthritidis could play a significant role in the inflammatory response induced in the host by this organism.
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Oliveira, Claudio, Paulo Mazzafera, Rosangela Silva, Roberto Kubo, Mario Inomoto, and Melissa Tomazini. "Pathogenicity of two Pratylenchus coffeae populations from Brazil on coffee plants." Nematology 9, no. 6 (2007): 853–58. http://dx.doi.org/10.1163/156854107782331144.
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AbstractThere is limited information on the influence of Pratylenchus coffeae on the growth and development of coffee plants, in spite of the widespread occurrence of this nematode in coffee plantations. In addition, populations of P. coffeae vary in morphological and molecular features, as well as reproductive fitness and pathological potential. The objective of the present study was to compare the pathogenicity of two Brazilian P. coffeae populations, K5 from Coffea arabica roots and M2 from Aglaonema sp. roots, in terms of their influence on the plant growth and photosynthesis of Arabian coffee (C. arabica). Five experiments were conducted in controlled conditions, and the results demonstrated that K5 is pathogenic on coffee, as it can reproduce and causes obvious damage on the plant. Moreover K5 proved to be very virulent on Arabian coffee, considering its effects on seedling mortality, plant growth and photosynthesis. By contrast, M2 was considered to be of low virulence, or even non-pathogenic, on coffee because it failed to reproduce. Thus, the results indicate that K5 and M2 may be distinct species, supporting the hypothesis of previous authors.
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Zhou, Ting, and Greg J. Boland. "Hypovirulence and Double-Stranded RNA in Sclerotinia homoeocarpa." Phytopathology® 87, no. 2 (1997): 147–53. http://dx.doi.org/10.1094/phyto.1997.87.2.147.
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One hundred and thirty-two isolates of Sclerotinia homoeocarpa, the causal agent of dollar spot of turfgrass, were evaluated for virulence on swards and detached leaves of creeping bentgrass and for the presence of double-stranded RNA (dsRNA). In at least four isolates, the hypovirulent phenotype was associated with the presence of specific segments of dsRNA. In addition, these hypovirulent isolates often grew slowly on potato dextrose agar (PDA), formed thin colonies with atypical colony margins, and failed to produce typical black stroma. The hypovirulent phenotype and dsRNA were transmitted from hypovirulent isolate Sh12B to virulent isolate Sh48B, and the converted isolate was hypovirulent and contained dsRNA. The hypovirulent phenotype and dsRNA also were transmitted to at least four other isolates of the pathogen, including the fungicide-resistant, dsRNA¯ isolate KY-7. Converted isolates of KY-7 developed the hypovirulent phenotype, grew on fungicide-amended medium, and contained dsRNA. Subcultures of hypovirulent isolate Sh12B that did not contain dsRNA were obtained through curative treatment using cycloheximide-containing medium and heat. Cured subcultures grew faster on PDA, had more typical colony morphologies, were more virulent on bentgrass leaves, and did not contain dsRNA. No cured subcultures were obtained from hypovirulent isolate Sh09B. Isolates regenerated from protoplasts of hypovirulent isolate Sh12B were not cured, remained hypovirulent, and contained dsRNA. Transmission of hypovirulence and dsRNA in S. homoeocarpa has potential as a novel approach to the management of dollar spot of turfgrass.
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Angkasekwinai, Pornpimon, Nuntarat Sringkarin, Oratai Supasorn, et al. "Cryptococcus gattii Infection Dampens Th1 and Th17 Responses by Attenuating Dendritic Cell Function and Pulmonary Chemokine Expression in the Immunocompetent Hosts." Infection and Immunity 82, no. 9 (2014): 3880–90. http://dx.doi.org/10.1128/iai.01773-14.
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ABSTRACTCryptococcal infections are primarily caused by two related fungal species:Cryptococcus neoformansandCryptococcus gattii. It is well known thatC. neoformansgenerally affects immunocompromised hosts; however,C. gattiiinfection can cause diseases in not only immunocompromised hosts but also immunocompetent individuals. While recent studies suggest thatC. gattiiinfection could dampen pulmonary neutrophil recruitment and inflammatory cytokine production in immunocompetent hosts, the impact ofC. gattiiinfection on the development of their adaptive T helper cell immune response has not been addressed. Here, we report thatC. neoformansinfection with highly virulent and less virulent strains preferentially induced pulmonary Th1 and Th17 immune responses in the host, respectively. However, fewer pulmonary Th1 and Th17 cells could be detected in mice infected withC. gattiistrains. Notably, dendritic cells (DC) in mice infected withC. gattiiexpressed much lower levels of surface MHC-II andIl12orIl23transcripts and failed to induce effective Th1 and Th17 differentiationin vitro. Furthermore, the expression levels ofIp10andCxcl9transcripts, encoding Th1-attracting chemokines, were significantly reduced in the lungs of mice infected with the highly virulentC. gattiistrain. Thus, our data suggest thatC. gattiiinfection dampens the DC-mediated effective Th1/Th17 immune responses and downregulates the pulmonary chemokine expression, thus resulting in the inability to mount protective immunity in immunocompetent hosts.
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Sugui, Janyce A., Julian Pardo, Yun C. Chang, et al. "Gliotoxin Is a Virulence Factor of Aspergillus fumigatus: gliP Deletion Attenuates Virulence in Mice Immunosuppressed with Hydrocortisone." Eukaryotic Cell 6, no. 9 (2007): 1562–69. http://dx.doi.org/10.1128/ec.00141-07.
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ABSTRACT Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the mycotoxin is not important for pathogenesis of A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on the pathobiological role of gliotoxin in two different mouse strains, 129/Sv and BALB/c, that were immunosuppressed by hydrocortisone alone to avoid neutropenia. These strains of mice were infected using the isogenic set of a wild type strain (B-5233) and its mutant strain (gliPΔ) and the the glip reconstituted strain (gliP R). The gliP gene encodes a nonribosomal peptide synthase that catalyzes the first step in gliotoxin biosynthesis. The gliPΔ strain was significantly less virulent than strain B-5233 or gliP R in both mouse models. In vitro assays with culture filtrates (CFs) of B-5233, gliPΔ, and gliP R strains showed the following: (i) deletion of gliP abrogated gliotoxin production, as determined by high-performance liquid chromatography analysis; (ii) unlike the CFs from strains B-5233 and gliP R, gliPΔ CFs failed to induce proapoptotic processes in EL4 thymoma cells, as tested by Bak conformational change, mitochondrial-membrane potential disruption, superoxide production, caspase 3 activation, and phosphatidylserine translocation. Furthermore, superoxide production in human neutrophils was strongly inhibited by CFs from strain B-5233 and the gliP R strain, but not the gliPΔ strain. Our study confirms that gliotoxin is an important virulence determinant of A. fumigatus and that the type of immunosuppression regimen used is important to reveal the pathogenic potential of gliotoxin.
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Ghannoum, Mahmoud A. "Potential Role of Phospholipases in Virulence and Fungal Pathogenesis." Clinical Microbiology Reviews 13, no. 1 (2000): 122–43. http://dx.doi.org/10.1128/cmr.13.1.122.
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SUMMARY Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.
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Torres, Alfredo G., Peter Redford, Rodney A. Welch, and Shelley M. Payne. "TonB-Dependent Systems of Uropathogenic Escherichia coli: Aerobactin and Heme Transport and TonB Are Required for Virulence in the Mouse." Infection and Immunity 69, no. 10 (2001): 6179–85. http://dx.doi.org/10.1128/iai.69.10.6179-6185.2001.
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ABSTRACT The uropathogenic Escherichia coli strain CFT073 has multiple iron acquisition systems, including heme and siderophore transporters. A tonB mutant derivative of CFT073 failed to use heme as an iron source or to utilize the siderophores enterobactin and aerobactin, indicating that transport of these compounds in CFT073 is TonB dependent. The TonB−derivative showed reduced virulence in a mouse model of urinary tract infection. Virulence was restored when the tonB gene was introduced on a plasmid. To determine the importance of the individual TonB-dependent iron transport systems during urinary tract infections, mutants defective in each of the CFT073 high-affinity iron transport systems were constructed and tested in the mouse model. Mouse virulence assays indicated that mutants defective in a single iron transport system were able to infect the kidney when inoculated as a pure culture but were unable to efficiently compete with the wild-type strain in mixed infections. These results indicate a role for TonB-dependent systems in the virulence of uropathogenic E. coli strains.
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Blankenship, Jill R., Floyd L. Wormley, Molly K. Boyce, et al. "Calcineurin Is Essential for Candida albicans Survival in Serum and Virulence." Eukaryotic Cell 2, no. 3 (2003): 422–30. http://dx.doi.org/10.1128/ec.2.3.422-430.2003.
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ABSTRACT Calcineurin is a calcium-activated protein phosphatase that is the target of the immunosuppressants cyclosporin A and FK506. In T cells, calcineurin controls nuclear import of the NF-AT transcription factor and gene activation. In plants and fungi, calcineurin functions in stress responses (e.g., temperature, cations, and pH) and is necessary for the virulence of the fungal pathogen Cryptococcus neoformans. Here we show that calcineurin is also required for the virulence of another major fungus that is pathogenic to humans, Candida albicans. C. albicans calcineurin mutants had significantly reduced virulence in a murine model of systemic infection. In contrast to its role in C. neoformans, calcineurin was not required for C. albicans survival at 37°C. Moreover, C. albicans calcineurin mutant strains exhibited no defects in known Candida virulence traits associated with host invasion, including filamentous growth, germ tube formation, and adherence to and injury of mammalian cells. C. albicans calcineurin mutant strains failed to colonize and grow in the kidneys of infected animals and were unable to survive when exposed to serum in vitro. Our studies illustrate that calcineurin has evolved to control aspects of the virulence of two divergent fungal pathogens via distinct mechanisms that can be targeted to achieve broad-spectrum antifungal action.
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Graybill, John R., Eleanor Montalbo, William R. Kirkpatrick, Michael F. Luther, Sanjay G. Revankar, and Thomas F. Patterson. "Fluconazole versus Candida albicans: A Complex Relationship." Antimicrobial Agents and Chemotherapy 42, no. 11 (1998): 2938–42. http://dx.doi.org/10.1128/aac.42.11.2938.
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ABSTRACT A murine model of systemic candidiasis was used to assess the virulence of serial Candida albicans strains for which fluconazole MICs were increasing. Serial isolates from five patients with 17 episodes of oropharyngeal candidiasis were evaluated. The MICs for these isolates exhibited at least an eightfold progressive increase from susceptible (MIC < 8 μg/ml; range, 0.25 to 4 μg/ml) to resistant (MIC ≥ 16 μg/ml; range, 16 to ≥128 μg/ml). Virulence of the serial isolates from three of five patients showed a more than fivefold progressive decrease in the dose accounting for 50% mortality and was associated with development of fluconazole resistance. Low doses of fluconazole prolonged survival of mice infected with susceptible yeasts but failed to prolong survival following challenge with a resistant strain. In addition, a decreased burden of renal infection was noted in mice challenged with two of the three resistant strains. This was consistent with reduced virulence. Fluconazole did not further decrease the level of infection. In the isolates with a decrease in virulence, two exhibited overexpression of CDR, which encodes an ABC drug efflux pump. In contrast, serial isolates from the remaining two patients with the development of resistance did not demonstrate a change in virulence and fluconazole remained effective in prolonging survival, although significantly higher doses of fluconazole were required for efficacy. Resistant isolates from both of these patients exhibited overexpression of MDR. This study demonstrates that decreased virulence of serial C. albicans isolates is associated with increasing fluconazole MICs in some cases but not in others and shows that these low-virulence strains may not consistently cause infection.
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Mee-Ngan, Yap, Jeri D. Barak, and Amy O. Charkowski. "Genomic Diversity of Erwinia carotovora subsp. carotovora and Its Correlation with Virulence." Applied and Environmental Microbiology 70, no. 5 (2004): 3013–23. http://dx.doi.org/10.1128/aem.70.5.3013-3023.2004.
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ABSTRACT We used genetic and biochemical methods to examine the genomic diversity of the enterobacterial plant pathogen Erwinia carotovora subsp. carotovora. The results obtained with each method showed that E. carotovora subsp. carotovora strains isolated from one ecological niche, potato plants, are surprisingly diverse compared to related pathogens. A comparison of 23 partial mdh sequences revealed a maximum pairwise difference of 10.49% and an average pairwise difference of 2.13%, values which are much greater than the maximum variation (1.81%) and average variation (0.75%) previously reported for Escherichia coli. Pulsed-field gel electrophoresis analysis of I-CeuI-digested genomic DNA revealed seven rrn operons in all E. carotovora subsp. carotovora strains examined except strain WPP17, which had only six copies. We identified 26 I-CeuI restriction fragment length polymorphism patterns and observed significant polymorphism in fragment sizes ranging from 100 to 450 kb for all strains. We detected large plasmids in two strains, including the model strain E. carotovora subsp. carotovora 71. The two least virulent strains had an unusual chromosomal structure, suggesting that a particular pulsotype is correlated with virulence. To compare chromosomal organization of multiple enterobacterial genomes, several genes were mapped onto I-CeuI fragments. We identified portions of the genome that appear to be conserved across enterobacteria and portions that have undergone genome rearrangements. We found that the least virulent strain, WPP17, failed to oxidize cellobiose and was missing several hrp and hrc genes. The unexpected variability among isolates obtained from clonal hosts in one region and in one season suggests that factors other than the host plant, potato, drive the evolution of this common environmental bacterium and key plant pathogen.
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Phan, Van, Robert Belas, Brendan F. Gilmore, and Howard Ceri. "ZapA, a Virulence Factor in a Rat Model of Proteus mirabilis-Induced Acute and Chronic Prostatitis." Infection and Immunity 76, no. 11 (2008): 4859–64. http://dx.doi.org/10.1128/iai.00122-08.
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ABSTRACT Our knowledge of pathogenesis has benefited from a better understanding of the roles of specific virulence factors in disease. To determine the role of the virulence factor ZapA, a 54-kDa metalloproteinase of Proteus mirabilis, in prostatitis, rats were infected with either wild-type (WT) P. mirabilis or its isogenic ZapA− mutant KW360. The WT produced both acute and chronic prostatitis showing the typical histological progressions that are the hallmarks of these diseases. Infection with the ZapA− mutant, however, resulted in reduced levels of acute prostatitis, as determined from lower levels of tissue damage, bacterial colonization, and inflammation. Further, the ZapA− mutant failed to establish a chronic infection, in that bacteria were cleared from the prostate, inflammation was resolved, and tissue was seen to be healing. Clearance from the prostate was not the result of a reduced capacity of the ZapA− mutant to form biofilms in vitro. These finding clearly define ZapA as an important virulence factor in both acute and chronic bacterial prostatitis.
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Mrochen, Daniel M., Liliane M. Fernandes de Oliveira, Dina Raafat, and Silva Holtfreter. "Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models." International Journal of Molecular Sciences 21, no. 19 (2020): 7061. http://dx.doi.org/10.3390/ijms21197061.
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Staphylococcus aureus (S. aureus) is a pathobiont of humans as well as a multitude of animal species. The high prevalence of multi-resistant and more virulent strains of S. aureus necessitates the development of new prevention and treatment strategies for S. aureus infection. Major advances towards understanding the pathogenesis of S. aureus diseases have been made using conventional mouse models, i.e., by infecting naïve laboratory mice with human-adapted S.aureus strains. However, the failure to transfer certain results obtained in these murine systems to humans highlights the limitations of such models. Indeed, numerous S. aureus vaccine candidates showed promising results in conventional mouse models but failed to offer protection in human clinical trials. These limitations arise not only from the widely discussed physiological differences between mice and humans, but also from the lack of attention that is paid to the specific interactions of S. aureus with its respective host. For instance, animal-derived S. aureus lineages show a high degree of host tropism and carry a repertoire of host-specific virulence and immune evasion factors. Mouse-adapted S.aureus strains, humanized mice, and microbiome-optimized mice are promising approaches to overcome these limitations and could improve transferability of animal experiments to human trials in the future.
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Tredway, L. P. "Genetic Relationships Among Magnaporthe poae Isolates from Turfgrass Hosts and Relative Susceptibility of ‘Penncross’ and ‘Penn A-4’ Creeping Bentgrass." Plant Disease 90, no. 12 (2006): 1531–38. http://dx.doi.org/10.1094/pd-90-1531.
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Isolates of Magnaporthe poae from turfgrass hosts were analyzed for mating type, genetic relatedness according to ITS sequences, reaction to a previously developed species-specific poly-merase chain reaction (PCR) assay, and virulence on two creeping bentgrass cultivars in growth chamber experiments. Analysis of internal transcribed spacer (ITS) sequences revealed three clades, designated A, B, and C. Clade A contained isolates of both mating types from creeping bentgrass, annual bluegrass, and Kentucky bluegrass. Clade B contained only mating type ‘A’ isolates from annual bluegrass, whereas Clade C contained only mating type ‘a’ isolates from creeping bentgrass. The M. poae PCR assay failed to positively identify several North Carolina isolates from annual bluegrass and creeping bentgrass. M. poae isolates from Kentucky blue-grass were most virulent toward creeping bentgrass in growth chamber experiments. Although isolates of M. poae are not host specific, certain ITS clades may have a limited host or geographical range. The improved creeping bentgrass cv. Penn A-4 was more susceptible to summer patch than cv. Penncross. Additional research is needed to develop methods for accurate diagnosis of summer patch and other patch diseases in creeping bentgrass and to determine how creeping bentgrass cultivars vary in their susceptibility to these root pathogens.