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1
Messad, Nourreddine. "Staphylococcus aureus colonisant / Staphylococcus aureus infectant dans le modèle du pied diabétique." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT063/document.
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Staphylococcus aureus est l’un des principaux agents étiologiques des infections suppuratives superficielles et profondes ainsi que des syndromes liés à l’action de toxines. Paradoxalement, cette bactérie est un agent commensal qui est présent sur la peau ainsi que dans les cavités nasales notamment. Cela permet de considérer cette bactérie comme un organisme colonisant commensale. Les bases génétiques expliquant la différence entre une bactérie pathogène et une bactérie commensale reste inconnues. En utilisant la technique Optical Maps sur des souches de S. aureus isolées de plaies de pieds diabétiques avec différents niveau de virulence, nous avons pu montrer l’existence d’un prophage insérés dans le génome des souches colonisantes et absent des souches infectantes. Le phage, nommé ROSA, est localisé dans un hotspot d’insertion de phage NM2. Il est aussi localisé en amont du locus isd qui est requis pour l’assimilation du fer essentiel à la bactérie dans sa phase pathogène. Le phage ROSA inactive la voie isd en dérégulant l’activité du régulateur transcriptionnel majeur Fur en absence de fer. Il réduit aussi la virulence de ces souches sur les 2 modèles de virulence (Le ver C. elegans et le Zebrafish). L’expulsion du phage ROSA restaure la régulation du locus isd par Fur et la production de sidérophores en absence de Fer, la formation du biofilm et la virulence des souches. La mutation du gène Fur nous a permis de déduire que le phage ROSA affectait les bactéries de manière indépendante de Fur. Enfin, nous avons étudié la prévalence des souches colonisantes sur les plaies de pieds diabétiques. Nous avons observé que 20% des souches présentait l’insertion ROSA et 89% appartenait au complexe clonal CC8. Les souches colonisantes, avec leur niveau bas de virulence, devraient faire l’objet de détection dans le but de rationnaliser l’utilisation des antibiotiques et ainsi lutter contre l’apparition de bactéries multirésistantes aux antibiotiques<br>Staphylococcus aureus is an opportunistic bacterium capable of causing a wide range of severe diseases when it gains access to underlying tissues. Paradoxically, this causative pathogen is a common inhabitant of the skin microflora and colonizes the nares and other human mucosa, and as such, may be considered as a commensal colonizing organism. The genetic basis for the differences in pathogenic/colonizing potential is unknown. By performing optical maps comparisons of a collection of S. aureus strains of defined virulence potential isolated from diabetic foot ulcers at different stages, we brought to light a prophage present in colonizing-causing bacteria. The phage, namely ROSA, was localized in a hotspot region NM2 near the locus isd, the main iron surface determinant that transport iron across the bacterial wall. It induces a deregulation of the activity of the transcriptional regulator Fur involving the biofilm formation of the bacteria in response to low iron environment. It reduced also significantly the virulence of the strain in two in vivo models (the nematode C. elegans and the zebrafish). The expulsion of the phage restored the regulation of the locus isd, the siderophore production, the biofilm formation and the virulence of the strain. The mutation of the fur gene within the colonizing strain enabled us to determine that the phage ROSA affect the the bacteria in a Fur-independent manner. Finally we determined the prevalence of these colonizing strains in skin and soft tissue infections (diabetic foot ulcers). We observed that 20% (39/195) of the strains harboured this insertion and 89% belonged to the clonal complex CC8. This colonizing strain by its low virulence potential must be detected in the aim to contribute to a sounder use of antibiotic treatment, an important point in front of the increase of multidrug resistant bacteria
2
Pourkomailian, B. "Osmoregulation in Staphylococcus aureus." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.593300.
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Osmoregulation in <I>Staphylococcus aureus </I>has been studied. Glycine betaine was found to act as an osmoprotectant by stimulating specific growth rate and salt tolerance of osmotically stressed <I>S. aureus </I>cells. The accumulation of this compatible solute was accomplished via two constitutive Na<SUP>+</SUP> dependant transport systems, a high-affinity system (Km = 3μM; Vmax = 26nmol. min<SUP>-1</SUP> mg total protein<SUP>-1</SUP>) and a low-affinity system (Km = 133μM; Vmax = 155 nmol. min<SUP>-1</SUP> mg total protein<SUP>-1</SUP>). The high-affinity system is specific for glycine betaine and its activity is not greatly stimulated by osmotic pressure. The low-affinity sytem transports proline and proline analogues and its activity is stimulated by increases in external osmolarity. Proline transport is achieved via two similar systems. Through transposon mutagenesis it was demonstrated that the low-affinity glycine betaine transport system and the low-affinity proline transport system are the same system. The low-affinity system is the major system responsible for the accumulation of glycine betaine. This is the more important system for the osmoregulation strategy of <I>S. aureus. </I>All three transport systems have been demonstrated to be subject to feedback regulation. The internal compatible solute concentration dictates the level of activity of the transport systems. A mutant has been isolated that lacks the low-affinity system and the high-affinity proline transport system.
3
Lucet, Jean-Christophe. "Epidémiologie de Staphylococcus aureus." Paris 11, 2004. http://www.theses.fr/2004PA114817.
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Ce travail a cherché à établir l'importance du réservoir méconnu des porteurs de Staphylococccus aureus résistant à la méticilline (SARM) dans l'épidémiologie hospitalière de cette bactérie multirésistante aux antibiotiques, la plus fréquente en France. Il montre au travers d'enquêtes prospectives, que la prévalence et l'incidence du SARM sont beaucoup plus elévées que ne laissent penser les surveillances basées sur des prélèvements à visée clinique. Il établit des facteurs de risque de portage de SARM, et suggère enfin que la stratégie de dépistage et précautions " contact " est efficace. Le contrôle de la dissémination manuportée du SARM doit inclure une stratégie raisonnée de dépistage des porteurs<br>Our research aimed to determine the significance of unknown carriage of methicillin-resistant Staphylococcus aureus in the epidemiology of this multiply-resistant strains in the hospital setting. Through prospective observational studies of MRSA carriage, we demonstrated that incidence and prevalence of MRSA at hospital admission are much higher than that estimated by clinical isolates only. We established parameters associated with MRSA carriage, and suggested that active surveillance screening and contact precautions are valuable in the ICU setting. Controlling the hospital spread of MRSA should include a judicious strategy for screening MRSA
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Zhang, Lihong. "Studies on protein Sbi in Staphylococcus aureus /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 2000. http://epsilon.slu.se/avh/2000/91-576-5780-7.pdf.
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Chaibenjawong, Plykaeow. "Desiccation Tolerance in Staphylococcus aureus." Thesis, University of Sheffield, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522502.
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Libberton, Andrew Benjamin. "The ecology of Staphylococcus aureus." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569556.
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Nasal carriage of Stephvtococcue aureus is associated with increased risk of infection in humans. Several factors are known to affect carriage including host genetics and S. aureus immune evasion. However while members of the microbial community have been shown to affect S. aureus nasal colonisation individually, relatively little work has been done to understand how and why nasal microbial community as a whole, affects carriage of S. aureus. Here, the cultivable bacteria from 60 anterior nares communities were sampled and identified to species level using apiSTAPH and 16S rRNA gene sequencing. The taxa distributions across communities revealed negative associations of S. aureus with the following taxa: S. capitis, Corynebacterium propinquum, C. macgin/eyi, Enterobacter aerogenes, S. epidermidis, Micrococcus sp., Bacillus sp., C. acco/ens, S. schleiferi and Gemella haemo/ysans. Since toxin-mediated interference can affect community composition, nasal isolates were screened for their ability to inhibit growth of S. aureus on a solid medium. Overlaying this inhibition data onto community taxa distributions revealed that negative associations between S. aureus and S. epidermidis, S. capitis, C. propinquum, C. acco/ens and a Micrococcus sp. were potentially driven by toxin- mediated interference competition. Moreover novel negative associates were found between S. aureus and an inhibitory subset of Micrococcus /uteus and S. hominis. By also measuring the cumulative inhibition of entire natural communities, it was possible to show that S. aureus was less frequent in highly inhibitory microbial communities. The quorum sensing mechanism, encoded by the agr locus, and biofilm formation have been proposed to play an important role in nasal colonisation of S. aureus. Therefore to further investigate community dynamics, S. capitis, S. epidermidis and corynebacteria isolates were assayed for their ability to interfere with Agr signaling and biofilm formation. No evidence was obtained to indicate that biofilm interference by these species affected the distribution of S. aureus across communities. By contrast, S. epidermidis isolates that interfered with Agr signaling were significantly more likely to coexist with S. aureus, and S. capitis isolates interfering with Agr signaling were significantly less likely to coexist with S. aureus. In theory, toxin-mediated interference competition can act both to protect producers against invasion, and, conversely, to promote the invasion of producers into an occupied niche. An experimental ecology approach was used to show that S. aureus is less likely to invade an inhibitor-producing S. epidermidis population than a non-inhibitor-producing population, especially on a spatially-structured medium. Furthermore, inhibitor-producing populations of S. epidermidis invade more successfully than non-inhibitor-producers, although they do not displace the S. aureus resident due to evolution of toxin resistance. There is also evidence of eo- evolution where inhibitor-producing strains of S. epidermidis can evolve stronger inhibitory activity when invading sensitive S. aureus populations that evolve resistance. These findings could impact the future treatment of S. aureus infections and help to control nasal carriage.
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Monk, Alastair Brian. "Staphylococcus aureus : evolution and epidemiology." Thesis, University of Bath, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413068.
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Jones, Eleanor. "Osmotic adaptations of Staphylococcus aureus." Thesis, University of Nottingham, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310928.
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Chaffey, Brian John. "The adhesion of Staphylococcus aureus." Thesis, University of Nottingham, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306699.
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Horsburgh, Malcolm James. "Chorismate synthase from Staphylococcus aureus." Thesis, University of Glasgow, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297034.
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Boldock, Emma. "Analysis of Staphylococcus aureus virulence." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/13835/.
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Reynaud-Rondier, Laure. "Antigènes glycoprotéiques de Staphylococcus aureus." Lyon 1, 1992. http://www.theses.fr/1992LYO10301.
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Notre travail porte sur une bacterie pathogene, staphylococcus aureus, qui intervient dans les infections humaines et animales. Le polysaccharide (ps) de s. Aureus etant un compose faiblement immunogene, son immunogenicite peut-etre nettement augmentee par le couplage a une proteine porteuse. L'originalite de notre etude reside dans l'utilisation d'un ps capsulaire et d'une proteine, l'hemolyse alpha, issus de la meme bacterie, ce qui devrait augmenter les proprietes antigeniques du conjugue. Nous avons donc forme des composes glycoproteiques en couplant par la methode au glutaraldehyde le ps de deux souches humaines aux hemolysines alpha des souches correspondantes. Apres avoir observe l'immunogenicite et l'antigenicite de conjugues produits a partir de composes partiellement purifies nous avons isole puis purifie les ps et les fractions hemolytiques et/ou antigeniques des deux souches de s. Aureus. L'etude structurale a permis d'identifier le ps 31 a un polymere d'acide aminogalacturonique lie en 1->4 et le ps 8914 a un polymere d'acide aminomannuronique lie en 1->3. Parmi les differents conjugues (ps-fraction proteique) obtenus, le produit couple homologue (ps-f42,5 kda) 8914 et le produit couple heterologue ps31-f42,5 kda 8914 se sont reveles les plus immunogenes et antigeniques mettant en evidence l'efficacite de la fraction proteique f42,5 de s. Aureus 8914 en tant que proteine porteuse. Les deux serums obtenus a partir de ces conjugues induisent une resistance contre s. Aureus 8914 chez la souris, celle-ci semble maximale dans le cas du serum heterologue. L. Reynaud-rondier, a. Voiland and g. Michel (1991). Fems microbiology immunology 76 193-200
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Piemont, Yves. "Les Exfoliatines de Staphylococcus aureus." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb37608872c.
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Zinsstag, Jakob. "Salmonellen Coagglutination mit Staphylococcus aureus /." [S.l : s.n.], 1985. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Beagle, Lucas K. "Synthesis and characterization of carbohydrate mimics /." Connect to resource online, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1219687360.
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Velasco, Valeria. "Detection and Molecular Typing of Methicillin-Susceptible Staphylococcus Aureus (MSSA) and Methicillin-Resistant Staphylococcus Aureus (MRSA)." Diss., North Dakota State University, 2015. http://hdl.handle.net/10365/24928.
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Methicillin-resistant (MRSA) and multidrug-resistant (MDR) Staphylococcus aureus, and the serotype (ST) 398 have been associated with human and livestock infections, being also detected in retail meat. The aim of this study was to determine the prevalence and molecular types of S. aureus strains from animals, retail raw meat, deli meat, and humans, determining the genetic similarity between the strains. A two-step selective enrichment followed by selective plating were used to isolate S. aureus from animals (n=167), retail raw meat (n=145), and deli meat (n=46). In addition, S. aureus from healthy people (n=550) was isolated by culture method. Positive isolates and MRSA isolates from clinical cases (n=108) were subjected to multiplex PCR (16S rRNA, mecA, and PVL genes), molecular typing and antimicrobial susceptibility testing. In addition, a real-time PCR assay was developed in order to decrease the time of detection of target genes of S. aureus in animal and meat samples, comparing the results with the standard culture/PCR method. The prevalence of S. aureus was 34.7% in animals, 47.6% in meat, and 13.0% in deli meat. The mecA gene was detected in S. aureus isolated from five pork meat samples and exhibited penicillin resistance. The ST398 was found in sheep, pigs, and pork meat. The S. aureus nasal carriage in healthy people was 7.6%. A total of 105 MRSA strains (97.2%) from clinical cases harbored the mecA gene and 11 (10.2%) the PVL gene. The rate of MDR was 70% in humans. A genetic similarity between strains from animals and meat, and from humans and meat was observed. Total agreement between the culture/PCR method and real-time PCR for detection of S. aureus was 68.9 to 97.8% (k=0.68-0.88), and the mecA gene, 86.7 to 98.7% (k=0-0.49). Therefore, the real-time PCR assay may be recommended as a rapid method for the detection of S. aureus, with confirmation of MRSA using the standard culture method. The presence of emerging S. aureus strains in the meat production chain and the genetic similarity between strains of different origin, suggests the contamination of meat, and a potential risk of transmission to humans.<br>Dean?s Office, College of Agriculture, Food Systems and Natural Resources, North Dakota State University
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Reinato, Lilian Andreia Fleck. "Colonização por Staphylococcus aureus em indivíduos com HIV/aids internados em um hospital escola do interior paulista." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/22/22132/tde-15012013-151405/.
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Introdução: a colonização de indivíduos com HIV/aids por microrganismos patogênicos tem sido associada a maior risco de morbidade e mortalidade, principalmente quando esse microrganismo é o Staphylococcus aureus. Identificar precocemente esta condição permite implementar medidas preventivas do adoecimento a ele relacionado, em nível individual e coletivo. Objetivo: avaliar a prevalência de colonização por Staphylococcus aureus em indivíduos com HIV/aids internados em um hospital escola. Metodologia: estudo de corte transversal, tendo como sujeito pessoas vivendo com HIV/aids, internadas em duas unidades especializadas em HIV/aids de um Hospital Escola do município de Ribeirão Preto- SP. Todos os preceitos éticos foram criteriosamente respeitados. No período de Agosto/2011 a Julho/2012, todos os indivíduos internados foram abordados e para aqueles que aceitaram participar, procedeu-se a coleta de amostra de saliva e secreção nasal, além da coleta de dados sociodemográficos, clínicos e imunológicos, obtidos por meio do prontuário e entrevista individual. As amostras foram encaminhadas e processadas pelo Laboratório de Microbiologia e Sorologia da instituição em estudo. Foram semeadas em meios de cultura ágar sangue e manitol, e após, transferidas para o sistema automatizado Vitek® 2 (BioMérieux(TM)), por meio dos cartões GP Test Kit Vitek® 2, para bactérias gram-positivas. Foram empregados cartões AST-P585 para avaliar a sensibilidade dos Staphylococcus aureus meticilina resistente (MRSA) aos antibióticos. Os dados foram armazenados em planilhas do Microsoft Office Excel 2011 for Mac e organizados por meio do software Statistical Package for the Social Sciences (SPSS), versão 17.0 for Windows. Resultados: De 229 indivíduos com HIV/aids internados nas unidades, 169 constituíram os sujeitos desta pesquisa, dos quais 57,4% eram do sexo masculino, 39,6% apresentaram idade de 40 a 49 anos e 45% tinham o primeiro grau completo. Foram obtidas 338 amostras (169 de secreção nasal e 169 de saliva). A prevalência de colonização por Staphylococcus aureus foi identificada em 20,4% das amostras, com 21,7% de resistência à oxacilina, sendo em secreção nasal 66,7% e em saliva 33,3%. Apresentaram contagem de linfócitos T CD4 abaixo de 200 células/mm3 60,0% dos indivíduos com MRSA nasal e 80,0% estavam em uso de antimicrobianos. Em 40,0% dos indivíduos com MRSA na saliva carga viral foi igual ou superior a 500.001 cópias/mL, e 80,0% destes também usavam antimicrobianos, MRSA nasal e saliva foi identificado em 60,0% dos indivíduos que não estavam em uso de antirretroviral. Conclusão: a prevalência de colonização por Staphylococcus aureus em indivíduos com HIV/aids foi predominante em secreção nasal, com baixa contagem de linfócitos T CD4, com história de internação prévia, uso de antimicrobiano e ausência do uso de antirretroviral, podendo representar importante fonte de infecção.<br>Introduction: colonization by pathogenic microorganisms in individuals with HIV/AIDS has been associated with increased risk of morbidity and mortality, especially when that organism is Staphylococcus aureus. Early identification of this condition allows implementing preventive measures of illness related to it, both individually and collectively. Objective: to evaluate the prevalence of Staphylococcus aureus colonization in individuals with HIV/AIDS in a teaching hospital. Method: cross-sectional study; the subjects were people living with HIV/AIDS and hospitalized in two specialized HIV/AIDS care units of a Teaching Hospital in the city of Ribeirão Preto. All ethical principles were carefully observed. In the period from August 2011 to July 2012, all subjects hospitalized were approached and, for those who agreed to participate, the collection of saliva and nasal discharge sample was performed, in addition to collecting sociodemographic, clinical and immunological data, obtained through medical record and individual interviews. The samples were forwarded and processed by the Laboratory of Microbiology and Sorology of the institution. They were seeded in blood agar and mannitol-salt-agar culture medium, and thereafter, transferred to the automated system Vitek® 2 (BioMérieux(TM)) through Vitek® 2 Test Cards for Gram-positive bacteria. AST-P585 cards were used to assess the sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) to the antibiotic. Data were stored in spreadsheets of Microsoft Office Excel 2011 for Mac and organized by the Statistical Package for the Social Sciences (SPSS) version 17.0 for Windows. Results: of the 229 individuals with HIV/AIDS hospitalized in the units, 169 were the subjects in this study, of whom 57.4% were male, 39.6% were aged from 40 to 49 years, and 45% had completed elementary school. 338 samples were collected (169 of nasal discharge and 169 of saliva). The prevalence of Staphylococcus aureus colonization was identified in 20.4% of samples, with 21.7% of oxacillin resistance, being 66.7% in nasal discharge and 33.3% in saliva. 60.0% of individuals with MRSA in nasal had lymphocytes T CD4 count below 200 cells/mm3 , and 80.0% were taking antimicrobials. In 40.0% of the individuals with MRSA in saliva, the viral load was equal or higher than 500.001 copies/mL, and 80.0% of these also used antimicrobials; MRSA in nasal and in saliva were detected in 60.0% of individuals who were not taking antiretroviral. Conclusion: the prevalence of Staphylococcus aureus colonization in individuals with HIV/AIDS was prevalent in nasal discharge, had lymphocytes T CD4 low count, with a history of previous hospitalization, antimicrobial use and the absence of antiretroviral use, and it may represent an important source of infection.
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Schmitt, Margrit Esther Scmitt Margrit Esther. "Temperaturabhängigkeit der Enterotoxinbildung bei Staphylococcus aureus /." [S.l.] : [s.n.], 1987. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=8230.
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Spaeth, Christoph. "Langzeitprognose der Bakteriämie mit Staphylococcus aureus /." Regensburg, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000254396.
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Mills, Bethany. "Molecular imaging of Staphylococcus aureus infections." Thesis, University of Nottingham, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.727640.
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Molecular imaging provides a less invasive means for studying bacterial infections in vivo compared to traditional techniques. However, molecular imaging of infection is currently limited due the lack of suitable imaging tracers. The most widely adopted approach for studying Staphylococcus aureus infections utilises a recombinant bioluminescent strain. However, several environmental requirements and signal attenuation through host tissue render this approach unsuitable for several applications. In order to provide an alternative research tool, the use of SNAP-tag, CLIP-tag and HaloTag was explored. Once expressed, these tags specifically bind fluorescent ligands. The tags were expressed via an inducible plasmid based system, and engineered to covalently attach to the cell surface of S. aureus. The function of the tags was validated in vitro by fluorescence imaging. SNAP-tag was subsequently incorporated into the genome of bioluminescent S. aureus Xen29. This thesis presents the first demonstration of visualising SNAP-tag expressing bacteria in vivo by fluorescent imaging. Potential applications for SNAP-tag imaging were then investigated; such as screening antimicrobials. Imaging of SNAP-tag expressing S. aureus was shown to provide additional information about the infection site compared to bioluminescence imaging alone. Novel [99mTc] SNAP-tag ligands were then developed and evaluated to provide a means for nuclear imaging of SNAP-tag. In addition, tools for infection diagnosis by nuclear imaging currently rely on targeting host immune responses rather than the bacteria directly; resulting in a high false positive rate. In order to develop a tracer with clinical potential to detect infection and not inflammation, the bacterial Universal Hexose Phosphate Transporter (UHPT) was selected as a target. [18F]FDG is an analogue of glucose and is widely used within nuclear medicine. [18F]FDG was phosphorylated, making it a substrate for UHPT. Validations in vitro suggested this probe may be a good tool for specific S. aureus detection; however in vivo biodistribution rendered it an unsuitable candidate.
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Li, Jun Wen. "Staphylococcus aureus heme acquisition from hemoglobin." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58518.
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Staphylococcus aureus is a bacterial pathogen of major health concern. Furthermore, the emergence of methicillin-resistant S. aureus (MRSA) strains limit the number of treatment options. Iron is essential for S. aureus survival and growth; however, the majority of iron in the human body is stored as hemoglobin (Hb) in erythrocytes. Hb released from lysed erythrocytes is quickly captured by serum haptoglobin (Hp) and the complex is degraded in the liver where released iron is then recycled. To date, the Iron Surface Determinant (Isd) system is the only heme utilization pathway identified in S. aureus. IsdB is the primary receptor at the cell surface that binds Hb to extract heme. Heme is then transferred to IsdA or IsdC, which then relay it to other Isd proteins for internalization. IsdB contains two NEAT (NEAr Iron Transporter) domains, and both domains and the intervening linker are needed for efficient heme uptake from Hb. In the first part of my study, the molecular mechanism of heme transfer from Hb to IsdB was investigated using site-directed mutagenesis. Residues in the heme-binding pocket were identified by inspection of a crystal structure of the complex of IsdB and Hb. The Y440F/Y444F (YFYF), E354A, M363L and S361A variants were found to be deficient in heme transfer. In particular, spectroscopic analysis of the YFYF mutant mixed with Hb provided evidence of a trapped heme transfer intermediate similar to that observed in the crystal structure of the wild-type protein. In the second part of my study, Hp was found to inhibit heme transfer from Hb to IsdB in a concentration-dependent manner and heme transfer was completely blocked when Hp was added to Hb above the binding stoichiometry determined by structural and solution studies. Moreover, Hb mixed with excess Hp did not support growth of S. aureus on iron-restrictive media. This study gained insight into the heme transfer mechanism between Hb and IsdB and revealed a novel role of Hp in blocking heme uptake by S. aureus.<br>Science, Faculty of<br>Microbiology and Immunology, Department of<br>Graduate
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Elgallali, Ashraf. "Characterisation of lipoproteins in Staphylococcus aureus." Thesis, University of Salford, 2016. http://usir.salford.ac.uk/38715/.
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The Gram-positive bacterium Staphylococcus aureus is an extremely successful opportunistic bacterium capable of causing a wide range of hospital-acquired and community-acquired infections, and is becoming increasingly virulent and resistant to antibiotics. In order to investigate this pathogen, various methods have been used to analyse the pathogenic behaviour including genomics, transcriptomics and proteomics. S. aureus expresses approximately 55-70 lipoproteins with only about half with known functions. Little is known about the biochemical functions of many individual lipoproteins and their proteomics has not been investigated in detail. Lipoproteins have a broad ranging functionality and perform various roles in bacterial activity and attract a particular interest to investigate their virulence and survival influences in the course of host infection. The initial part of this study was to find out whether the lipoproteins of S. aureus have similar genetic characteristics among all strains. PCR and Quantitative Real-Time PCR experiments were performed to analyse the genetic and the expression levels for some lipoprotein genes. The majority of PCR results showed high similarity in lipoprotein genetic structure among the examined strains. Phylogenetic trees from concatenated lipoprotein genes alignment were generated to represent the lipoprotein genes distribution of S. aureus strains. To identify and characterise proteomic of S. aureus lipoproteins a comprehensive quantitative proteome profiling of S. aureus lipoproteins using gel-free /in-solution trypsin digestion system followed by LC-MS/MS quantification identified 38 lipoproteins that represent two-thirds of the S. aureus MRSA252 lipoprotein. In addition, S. aureus-mediated infections with live C. elegans were performed on solid assays to investigate the host-pathogen relationships. S. aureus MRSA252 exhibited a high level of nematocidal activity with average time for half of the worms to die of ~ 2 d and infected C. elegans showed visible signs of illness. To evaluate lipoprotein transcripts expression level and microbe/host-specific pathogenic factors RNA of both S. aureus and C. elegans were characterised after isolation from the infected C. elegans and subjected to RNA Sequencing, the large-scale data has provided useful information on pathogen and host activities during infection. RNA sequencing analysis showed different types of regulations and interactions of lipoprotein transcripts during host exposures to indicate 3 transcripts significantly were up-regulated and 11 down-regulated. RNA sequencing analysis showed that 62 lipoprotein transcripts were expressed during C. elegans infection model. Proteomic analysis using the application of gel-free proteomic technique identified 38 lipoproteins that were expressed in the non-infection condition representing approx. two-thirds of the S. aureus MRSA252 lipoproteins. The results suggest that some lipoproteins were involved in pathogenesis of C. elegans but their function were not clear. More research is needed for explore the roles of lipoproteins in pathogenesis and the interactions of S. aureus with the host immune responses.
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Evans, Jane E. "The conjugation system of Staphylococcus aureus." Thesis, University of Oxford, 1986. https://ora.ox.ac.uk/objects/uuid:1c1f5c11-f854-4af5-b9cf-34fdf279fb28.
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A conjugation system in Staphylococcus aureus has been investigated and shown to be determined, at least in part, by genes carried on plasmids. Conjugation required cell-to-cell contact but not calcium ions. The frequency of conjugation depended on the recipient used and on the incubation conditions. Two conjugative plasmids were mapped by restriction enzyme analysis but experiments to clone the conjugation-determining region were unsuccessful although separate regions specifying gentamicin resistance, ethidium bromide resistance and cadmium resistance were cloned. The gentamicin resistance determinant was probably part of Tn4001. Deletion of various sized pieces of DNA from one of the plasmids resulted in reduction of its ability to specify conjugation but no specific part of this plasmid could be implicated in the process. Further experiments led to the conclusion that this particular plasmid (p8325-4) is probably not self-transmissible but transferred by a phage-mediated system. Strains of Staphylococcus aureus produced a pheromone-like substance that elicited a clumping response in Streptococcus faecalis but no evidence was found for the involvement of staphylococcal conjugative plasmids in this. The conjugative plasmid, p8325-2, mobilized a small plasmid (pT181) but not a chromosomal gene. Insertion of transposon Tn551 was used to produce mutants of the conjugative plasmid p8325-2. Some twenty-six mutants were studied and the position of Tn551 in them mapped. There were preferred regions of insertion for Tn551 and twenty out of the twenty-six mutants had altered ability to conjugate. One showed a significantly higher frequency of conjugation and the other nineteen, all with substantially lower frequencies of conjugation, were mapped to two well-separated regions of the plasmid. Similarity between the locations of these putative regions and those reported for some other conjugative plasmids from staphylococci is striking and suggests a common origin.
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Collins, James T. "Staphylococcus aureus toxins : expression and control." Thesis, University of Oxford, 2009. https://ora.ox.ac.uk/objects/uuid:b1226c5f-aedc-413f-8af4-9fb619c2de24.
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Staphylococcus aureus was discovered in 1880 by the Scottish surgeon Sir Alexander Ogston. Its ability to utilise a panoply of secreted and cell associated virulence factors, combined with an ability to rapidly adapt to antibiotic selective pressure, has led it to become one of the most important Gram positive pathogens of our time. It plays a significant role in chronic diseases such as eczema, as well as the acute and potentially life threatening conditions toxic shock syndrome (TSS), meningitis, pneumonia and staphylococcal scalded skin syndrome (SSSS) to name just a few. Its presence in hospitals is endemic in many countries, where methicillin resistant S. aureus (MRSA) strains have earned the 'superbug' moniker. Using a large, well-defined, clinical strain collection in combination with isogenic lab strains, this study endeavored to characterise the genetic factors associated with S. aureus toxicity, and identify novel means of controlling toxin expression. We found that: • A broad range of toxicities exists among S. aureus strains, that the beta- and delta-haemolysins are involved, and that hospital acquired-MRSA (HA-MRSA) strains are less toxic than MSSA or community acquired-MRSA (CA-MRSA). • NaCl and the emollient Oilatum downregulate toxin expression. • The mecA gene, conferring methicillin resistance, mediates mutation rates. • The large type II SCCmec element of HA-MRSA confers a significant metabolic burden which is mitigated by the down regulation of toxins. • The smaller type IV SCCmec element of CA-MRSA does not confer a significant metabolic burden, enabling CA-MRSA to utilise their full arsenal of virulence factors.
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Spanoudis, Catherine M. "Cell Division Regulation in Staphylococcus aureus." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7090.
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Cell division is a fundamental biological process that occurs in all kingdoms of life. Our understanding of cell division in bacteria stems from studies in the rod-shaped model organisms: Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. The molecular underpinnings of cell division regulation in non-rod-shaped bacteria remain to be studied in detail. Rod-shaped bacteria possess many positive and negative regulatory proteins that are essential to the proper placement of the division septa and ultimately the production of two identical daughter cells, many of which are absent in cocci. Given that essential cell division proteins are attractive antibacterial drug targets, it is imperative for us to identify key cell division factors especially in pathogens, to help counter the emergence of multi-drug resistance. In Staphylococcus aureus, a spherical Gram-positive opportunistic pathogen that causes a range of diseases from minor skin infections to life-threatening sepsis, we have identified the role of an essential protein, GpsB, in the regulation of cell division. We discovered that GpsB preferentially localizes to cell division sites and that overproduction of GpsB results in cell enlargement typical of FtsZ inhibition, while depletion of GpsB results in cell lysis and nucleoid-less minicell formation. The identification of GpsB’s interaction partners will allow us to understand the molecular mechanism by which GpsB regulates cell division.
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Browne, C. "Plasmid-chromosomal interactions in Staphylococcus aureus." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355715.
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Walters, John Anthony. "Replication of plasmids of Staphylococcus aureus." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.315767.
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Lowder, Bethan Victoria. "Host-adaptive evolution of Staphylococcus aureus." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/6209.
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Staphylococcus aureus is a notorious human pathogen associated with severe nosocomial and community-acquired infections. In addition, S. aureus is a major cause of animal diseases including skeletal infections of poultry and bovine and ovine mastitis, which are a large economic burden on the broiler chicken and dairy farming industries. The population structure of S. aureus associated with humans has been well studied. However, despite the prevalence of S. aureus infections in broiler flocks, our understanding of the diversity of poultry S. aureus is very limited. In this study, multilocus sequence typing was performed on 48 strains of S. aureus isolated from broiler chickens on farms in 6 countries on 4 different continents, in addition to 9 isolates from different species of reared game and wild birds in Scotland. This was followed by fine scale population genetic analysis of a subset of strains by single nucleotide polymorphism discovery. These studies reveal that the majority of S. aureus isolates from broiler chickens are the descendants of a single human-to-poultry host jump by a subtype of the worldwide human clonal complex 5 (CC5) clonal lineage unique to Poland. In contrast to human subtypes of the CC5 radiation, which demonstrate strong geographic clustering, the poultry CC5 clade was distributed in different continents, consistent with wide dissemination via the global poultry industry distribution network. In order to establish the molecular basis for avian specificity in the CC5 poultry clade, whole genome sequences were determined for a sequence type 5 (ST5) poultry isolate from Ireland and a basal human associated ST5 MRSA strain from Poland. Sequence analysis revealed that the poultry CC5 clade has undergone genetic diversification from its human progenitor strain by acquisition of novel mobile genetic elements from an avian-specific accessory gene pool, and by the inactivation of several proteins important for human disease pathogenesis. In order to examine the importance of positive selection in the adaptation of S. aureus to poultry and for S. aureus evolution, in general, genome-wide analysis of the ratio of synonymous to non-synonymous substitutions was performed on 30 strains from 3 humans and other animals, from diverse lineages. Positive selection has affected proteins from the majority of functional categories, resulting in diversification of the proteome, metabolome and replication capacity, which may be associated with adaptation of S. aureus to diverse environments. For several proteins, an elevated rate of non-synonymous substitutions unique to animal-associated lineages is consistent with a role for these proteins in host adaptation. Taken together, the results of this study have determined the evolutionary history of a major new animal pathogen that has undergone rapid avian host adaptation and intercontinental dissemination. The data highlight the importance of gene acquisition and loss and positive selection in the adaptive evolution of S. aureus.
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McAulay, Kathrine. "Glycosylation of Staphylococcus aureus surface proteins." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555122.
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Staphylococcus aureus is a major human pathogen, causing a wide spectrum of superficial and systemic infections. With the advent of methicillin resistant Staphylococcus aureus (M RSA) and the increasing spread of antibiotic resistance it has become clear that novel approaches must be taken to control S. aureus. Glycosylation, the modification of proteins with carbohydrate moieties, was long considered a process confined to eukaryotes; however, the last 3 decades have seen increasing awareness and characterisation of glycosylation systems in bacteria, including many pathogens In this study S. aureus strains were found to express several glycoproteins, covalently anchored to the cell wall peptidoglycan, including Cif A, Pis and putatively SdrC, SdrD and Clfb. CIf A glycosylation was readily detected and the glycosyltransferase enzymes responsible for Cif A modification (GtfA and GtID) were found to be encoded in a separate chromosomal location from cl(A. MALDI-MS/MS and GC-MS experiments revealed the presence of hexose and terminal HexNAc residues, consistent with an observed affinity for concanavalin A (ConA) and wheatgerm agglutinin (WGA) lectins. ConA affinity was then utilised to localise CIf A on the surface of S. aureus cells using a lectin-fluorophore conjugate, revealing a punctate presence of glycosylated protein around the cell wall. Glycosylation of CIf A was found to have no effect on fibrinogen (Fg) binding, however a role has been revealed in infection in a murine model of septic arthritis. A strain deficient in c/fA was highly attenuated in this model, whereas a strain deficient in both c/fA and gtfAB resulted in infection similar to the wild type. This data suggests a role for glycosylation in anti-virulence and thus has provided a novel insight into the nature of the host-pathogen interaction. Also, glycosylated CIf A was found to react with human sera at a significantly higher level than recombinant protein. The results highlight potential new avenues concerning immunological approaches to the control of S. aureus.
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Miller, Ruth. "Staphylococcus aureus : the host-organism relationship." Thesis, University of Oxford, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555258.
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Staphylococcus aureus is a worldwide leading cause of skin and soft tissue, bone and joint, and bloodstream infection. Despite this, S. aureus is also a harmless commensal in about one third of the population, although carriage is a risk factor for subsequent disease. S. aureus has evolved resistance to several antibiotics, including meticillin, resulting in meticillin-resistant S. aureus (MRSA), which in the UK largely consists of two epidemic lineages. In spite of much research, substantial aspects of the epidemiology and biology of S. aureus are still poorly understood. In investigating the S. aureus host-organism relationship, this thesis has three aims. To explore the interface between community and hospital-acquired S. aureus; to investigate the carriage dynamics of S. aureus in the community; and to use population genetic methods to study epidemic hospital associated S. aureus lineages. Case-control studies comparing hospital and community-acquired MRSA revealed that the majority of UK MRSA remains healthcare associated, with community-acquired MRSA reliably identified in only 0.2% of individuals. However, an additional 0.2% of individuals also carried "feral" MRSA with molecular characteristics identical to hospital-associated strains, but in hosts with no healthcare risk factors. To further investigate S. aureus carriage dynamics in the community, a carriage study was designed to collect detailed host factor information and correlate this with S. aureus carriage over time. In the study 32% of participants carried S. aureus of which the majority carried for over one year. Younger age was associated with transient carriage, including S. aureus acquisition in individuals who were initially negative. Finally, whole-genome sequencing of two epidemic S. aureus lineages indicated rapid clonal expansion of MRSA and clear geographic and temporal genetic structure. One particularly closely related cluster of strains may provide a genetic explanation for an MRSA outbreak in Brighton.
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El, Haddad Lynn. "Caractérisation des phages de Staphylococcus aureus." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/27502/27502.pdf.
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Wharton, Stephen J. "Metal ion homeostasis in Staphylococcus aureus." Thesis, University of Sheffield, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392723.
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Harris, Llinos Gwawr. "Molecular analysis of Staphylococcus aureus adhesins." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269271.
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Wootton, Mandy. "Intermediate vancomycin resistance in Staphylococcus aureus." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409009.
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Sharma, Hema. "Staphylococcus aureus and toxic shock syndrome." Thesis, Imperial College London, 2016. http://hdl.handle.net/10044/1/61350.
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Staphylococcal toxic shock syndrome (TSS) was originally described in menstruating women using high-absorbency tampons and linked to toxic shock syndrome toxin (TSST)-1 producing Staphylococcus aureus. Few studies have investigated the pathogenesis and treatment of TSS and contemporary clinical and moleculo-epidemiological descriptions are lacking. Clinical and molecular analysis of 180 TSS referalls to the UK reference laboratory between 2008-2012 was undertaken. Average annual TSS incidence was 0.08/100,000 population. Most cases were non-menstrual (nmTSS), related to skin and soft tissue infections and caused by tst+ clonal complex (CC) 30 MSSA. tst+ CC30 MRSA rarely caused TSS. Focussing on tst+ CC30 clinical strains, MSSA isolates produced more TSST-1 and superantigenic activity than MRSA isolates in vitro. A non-synonymous mutation in a tst regulator ccpA, ILE87, was detected in 33/39 CC30 MRSA strains that was associated with reduced TSST-1 production in vitro and SCCmecII. A murine abscess model of nmTSS was developed using tst+ CC30 S. aureus in TSST-1-sensitive transgenic HLA-DQ8 mice. Bacteria were detected in abscesses, lymphoid organs and blood. TSST-1 was detected in abscesses and draining lymph nodes, with detectable serum superantigen bioactivity. Mirroring in vitro findings, CC30 MSSA strains produced more TSST-1 in abscesses, and abscess and serum superantigenicity, than CC30 MRSA strains. TSST-1 expanded T cell Vβ subsets 3 and 13 in HLA-DQ8 mice. IL-6, IFNγ, KC and MCP-1 were consistently raised during infection. Clindamycin-containing antimicrobial regimens reduced abscess size and TSST-1 production. TSS in the UK is mainly non-menstrual and caused by tst+ CC30 MSSA strains producing more TSST-1 and superantigenic activity than MRSA counterparts. MRSA-TSS is extremely rare, perhaps due to altered tst regulation and diminished TSST-1 production. Clindamycin impaired TSST-1 production, supporting lincosamide use in treatment. This new nmTSS model should provide novel insight into S. aureus pathogenesis, especially TSST-1 production in situ within local lymphoid tissue.
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Gómez, Serrano Amalia. "Studies on pbp2 of Staphylococcus aureus." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624442.
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Deschênes, Elaine. "Vaccination à l'ADN contre Staphylococcus Aureus." Mémoire, Université de Sherbrooke, 2004. http://savoirs.usherbrooke.ca/handle/11143/4640.
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Staphylococcus aureus est une bactérie qui possède un potentiel virulent très élevé. Elle cause plusieurs types d’infections telle que des septicémies, des endocardites, et des mammites. La mammite bovine à Staphylococcus aureus est une infection très affligeante pour les animaux et les producteurs laitiers touchés. Ses nombreux facteurs de virulence permettent à la bactérie d’infecter les glandes mammaires des animaux en lactation. Il n’existe toujours pas de vaccins efficaces pour combattre ou prévenir les infections à Staphylococcus aureus. Il est donc primordial de trouver de nouvelles approches de vaccination. La vaccination à l’ADN apporte un nouvel espoir de vaccination bénéfique pour le combat de ces infections. Ce projet avait pour objectif de tester, dans un modèle murin, l’efficacité de certains antigènes à induire chez la souris une réponse immunitaire efficace et protectrice contre Staphylococcus aureus. Nous avons choisi des antigènes impliqués dans la virulence de la bactérie en supposant que ces derniers nous permettent d’avoir un vaccin génique efficace contre Staphylococcus aureus. Nous avons donc construit des plasmides pour les vaccins contenant nos gènes d’intérêt soit la séquence codant pour la Sortase et le peptide auto-inducteur, deux protéines impliquées dans la virulence de la bactérie. Deux autres antigènes ont été inclus dans nos expérimentations. Ces antigènes sont le « dumping factor A » (Clfa) et la « fibronectin-binding-protein A », deux adhésines liant le fibrinogène et la fibronectine respectivement. Nous avons pu obtenir une réponse humorale significative contre les antigènes Clfa, la Sortase et le peptide autoinducteur et une réponse cellulaire significative contre l’antigène Clfa. Un effet de protection statistiquement significatif contre une infection expérimentale avec un vaccin contenant quatre plasmides codant pour chacun des antigènes mentionnés plus haut a également été observé. Ces résultats suggèrent de poursuivre les recherches avec ces antigènes.
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Faria, Rafael César Bolleli. "Resistência a antimicrobianos em Staphylococcus aureus." Universidade Federal de Uberlândia, 2008. https://repositorio.ufu.br/handle/123456789/15785.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior<br>Multiple antibiotic resistant Staphylococcus aureus represent a big problem
in the control of hospital infections. Resistance pattern of isolated S. aureus
presented in central vascular catheter of patients interned in the Intensive Therapy
Center of the School Hospital of the Universidade Federal do Triângulo Mineiro
was evaluated by antimicrobial tests, in which it was possible to detect high level
of resistance to penicillin (94.7%) and ampicillin (86.8%), only considering the
samples that presented resistance, beyond one strain that presented resistance to
vancomycin. The oxacillin resistance evaluation was confirmed by PCR with the
presence of the gene mecA. The association of the results obtained in the
phenotypic test with the presence of the gene mecA, considered the reference
method, was confirmed through the Table of Contingency and the Test of Χ2 with
Yates correction. In 49 isolates evaluated, 23 were resistant to oxacillin, being
possible to detect the mecA gene in 21 samples. The test of molecular screening
by RAPD allowed the separation of the phenotypic groups in two different grouping
patterns, the ones that presented resistance to antimicrobials and the sensible
ones, with a dissimilarity of 73,3%. There is a higher genetic similarity between
groups that present the same type of resistance, thus confirming the phenotypic
analyses. Molecular markers for detection of resistance to oxacillin, like the gene
mecA, were more sensitive than the phenotypic markers.<br>Staphylococcus aureus resistentes a múltiplos antibióticos representam um
grande problema no controle das infecções hospitalares. O perfil de resistência a
antimicrobianos de isolados de S. aureus presentes em cateteres vasculares
central de pacientes internados em leitos do centro de terapia intensiva do
Hospital Escola da Universidade Federal do Triângulo Mineiro foi avaliado por
meio de testes antimicrobianos, pelos quais foi possível detectar um elevado nível
de resistência à penicilina (94,7%) e ampicilina (86,8%), considerando-se
somente as amostras que possuíam resistência, além de uma cepa resistente à
vancomicina. A avaliação da resistência à oxacilina foi confirmada por PCR
através da presença do gene mecA. A associação dos resultados obtidos no teste
fenotípico com a presença do gene mecA, considerado um método de referência,
foi confirmada através da Tabela de Contingência e do Teste de Χ2 com correção
de Yates. Em 49 amostras avaliadas, 23 apresentaram resistência à oxacilina,
sendo possível detectar a presença do gene de resistência mecA em 21
amostras. O teste de tipagem molecular por RAPD permitiu a separação dos
grupos fenotípicos em dois padrões diferentes de agrupamento, os que possuíam
resistência e os sensíveis aos antimicrobianos, com uma dissimilaridade de
73,3%. Há maior similaridade genética entre grupos que apresentam o mesmo
tipo de resistência, confirmando assim as análises fenotípicas. Marcadores
moleculares para detecção de resistência à oxacilina, como o gene mecA, foram
mais sensíveis que os marcadores fenotípicos.<br>Mestre em Genética e Bioquímica
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Weiss, Andy. "Non-classical regulators in Staphylococcus aureus." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/6779.
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Staphylococcus aureus is a highly problematic human pathogen due to its ability to cause devastating infections, paired with a capacity to withstand the action of a large fraction of available antibiotics. Both pathogenicity and antibiotic resistance are encoded by numerous genomic elements, though the expression of these factors is energetically costly and not always beneficial for cellular survival. Therefore, S. aureus has developed sophisticated regulatory networks to integrate a multitude of signals, enabling it to navigate the delicate balance between its pathogenic lifestyle and baseline needs for cellular energy homeostasis. It is thus imperative to study S. aureus behavior and its underlying regulatory circuits not as isolated entities, but rather holistically as part of an optimized, highly interconnected system. To do so, we must seek to achieve a comprehensive understanding of all encoded regulators, that is, not only historically well defined elements like transcription factors, two-component systems and σ factors, but also the lesser studied ’non-classical’ regulators like small regulatory RNAs and regulatory subunits of RNA-dependent RNA polymerase (RNAP). To this end, we describe here the identification of numerous, previously unidentified sRNAs and their incorporation into a new standardized cataloging and annotation system. The identification and annotation procedures are based on a number of RNAseq experiments performed in three different S. aureus backgrounds (MRSA252, NCTC 8325, and USA300). We then apply RNAseq to evaluate the expression patterns of these elements when grown in human serum, thus probing for possible connections between sRNAs and S. aureus pathogenicity. In addition, we characterize the role of two small RNAP subunits, δ and ω, for S. aureus RNAP function. δ is of particular interest, as it is unique to Gram-positive bacteria; deletion of the subunit results in a loss of transcriptional stringency and decreased expression of numerous virulence determinants. These alterations are accompanied by impaired survival of the δ mutant in whole human blood, increased phagocytosis by human leukocytes, and decreased survival in a murine model septicemia when compared to its parental strain. In contrast, there is no indication of direct and gene-specific transcriptional functions for ω. Rather, we describe a role for ω in the structural integrity of the RNAP complex, where its loss leads to a structural disturbance in the RNAP complex that causes altered affinities for (alternative) σ factors and the δ subunit. Overall, the findings presented here contribute to a better understanding of the intricate regulatory systems that guide the lifestyle of an organism that presents an immense burden to patients and our health care system alike.
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Connolly, John. "Analysis of Staphylococcus aureus virulence determinants." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/12109/.
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The success of the pathogen Staphylococcus aureus lies in its array of virulence determinants, which enable pathogenesis. The recent identification of novel S. aureus virulence determinants led to the hypothesis that there are more to be found. In silico analysis of the S. aureus genome identified three staphylococcal superantigen-like proteins (SSL12, SSL13 & SSL14), incorrectly annotated in the genome database as hypothetical proteins. Production of recombinant SSL12, 13 & 14 proteins gave a low yield of soluble protein, which precluded biochemical analysis. A genetic approach was taken and a triple gene deletion mutant constructed. No role for the 3 SSLs was found in an in vivo infection model, or in in vitro phagocytosis assays. However, a subtle reduction in growth in human blood, associated with the cellular component of blood was seen when compared with the wild-type. A genome-wide library of 1,920 strains each with a separate gene disrupted by a transposon (Tn) insertion was screened on human blood agar. Both the purine (purA and purB) and tetrahydrofolate (THF; pabA) synthesis pathways were found to be important for growth on human blood, but, in the case of the pabA disrupted strain, not on human plasma. THF is a single carbon donor/acceptor in many S. aureus biosynthesis pathways, and its synthesis is the target of sulphonamide antibiotics. The human blood phenotype for pabA was linked to dTTP synthesis, which is formed via a THF-dependent pathway, or a THF-independent pathway requiring the enzyme Tdk. As the pabA mutant can grow on human plasma it was hypothesised that Tdk is inhibited by a factor in the cellular component of blood, which leads to a requirement for dTTP. This suggests that the activity of sulphonamide drugs is the result of inhibition of THF coupled with the inhibition of Tdk by an as yet unknown factor present in human blood.
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Evans, Michael R. "Labeled mimics of N-Acetyl-D-Fucosamine /." Connect to resource online, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1210527108.
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Venâncio, Paulo César 1966. "Composição química e atividade antimicrobiana e de extratos à base de alho (Allium sativum e Allium tuberosum) sobre a infecção estafilocócica = estudo in vitro e in vivo, em ratos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288948.
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Orientador: Francisco Carlos Groppo<br>Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba<br>Made available in DSpace on 2018-08-17T06:56:23Z (GMT). No. of bitstreams: 1
Venancio_PauloCesar_D.pdf: 2224569 bytes, checksum: 664ae2a7eae028761da8674cbbd97e5f (MD5)
Previous issue date: 2010<br>Resumo: Este estudo teve por objetivo avaliar a atividade antimicrobiana de soluções de alho ( Allium tuberosum e Allium sativum) sobre a infecção estafilocócica em ratos e observar suas respectivas composições químicas. A atividade antimicrobiana in vitro das soluções foi analisada pelos testes de concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM), contra a mesma cepa utilizada in vivo, e a análise da composição química dos extratos foi feita por cromatografia gasosa. Esponjas de policlorovinil (PVC) foram implantadas no dorso de 95 ratos. Após 14 dias, os granulomas formados foram infectados com Staphylococcus aureus ATCC 25923. Após 24h da infecção, os animais foram divididos aleatoriamente nos seguintes grupos: Grupo 1 - Controle A (soro fisiológico); Grupo 2 - A. sativum 100mg/kg; Grupo 3 - A. sativum 400mg/kg; Grupo 4 - A. tuberosum 100mg/kg; Grupo 5 - A. tuberosum 400mg/kg; e Grupo 6 - Amoxicilina 50mg/kg. Os animais receberam os tratamentos por via oral a cada 6 horas. Cada grupo foi dividido em três subgrupos de cinco animais cada, os quais foram mortos após 6, 12 e 24 horas, respectivamente. No Grupo 1, também foi utilizado um grupo que foi morto no tempo "zero", isto é, logo após a primeira administração do soro fisiológico. Os granulomas retirados foram acondicionados em tubos de ensaio, recebendo agitação em vórtex e a suspensão resultante foi cultivada em meio de cultura agar sal e manitol (SMA). Após 18 horas, os microrganismos foram contados manualmente. Os resultados foram comparados através do teste de Kruskal-Wallis, com nível de significância de 5%. A análise cromatográfica mostrou que a composição química foi diferente nos dois extratos, e apresentou compostosorgânicos e organossulfurados, provavelmente resultantes da degradação da alicina. Os testes de sensibilidade CIM e CBM revelaram que a solução de A. tuberosum não mostrou capacidade de inibir ou matar a cepa de S. aureus em nenhuma das concentrações utilizadas. Entretanto, o A. sativum mostrou CIM de 2mg/mL e CBM de 4mg/mL. De uma maneira geral, o peso dos granulomas no ix grupo controle foi menor (Kruskal-Wallis, p<0,05) do que nos demais grupos, considerando-se cada tempo separadamente, sendo que nos tempos 12h e 24h, o A. tuberosum mostrou maior peso do que os demais grupos. Foi possível observar que houve diminuição da concentração de UFC/mL após 24 horas para todos os grupos. Nos grupos amoxicilina e A. sativum 400mg/kg, esta redução ocorreu a partir de 12 horas. De uma maneira geral, todos os tratamentos causaram redução significativa quando comparados ao grupo controle em todos os períodos de tempo. Além disso, não houve diferenças estatisticamente significantes entre a quantidade de bactérias recuperadas do grupo amoxicilina e os demais tratamentos no período de 24 horas. Concluímos que os extratos foram capazes de inibir a infecção estafilocócica nos animais de maneira similar à amoxicilina<br>Abstract: The aim of this study was to observe the chemical composition and to evaluate the antimicrobial activity of garlic ( Allium tuberosum and Allium sativum) extracts against staphylococcal infection induced in rats. The in vitro antimicrobial activity was obtained by the minimum inhibitory (MIC) and bactericidal (MBC) concentrations against the same strain used in the in vivo assay. The chemical composition of the extracts was measured by gas chromatography. Polyclorovinyl (PVC) sponges were implanted on the backs of 95 rats. After 14 days, the resulting granulomas were infected with Staphylococcus aureus ATCC 25923. After 24 hours of infection, the animals were divided randomly into four groups: Group 1 - The Control (saline), Group 2 - A. sativum 100mg/kg/p.o., Group 3 - A. sativum 400mg/kg/p.o., Group 4 - A. tuberosum 100mg/kg/p.o., Group 5 - A. tuberosum 400mg/kg/p.o. and Group 6 - Amoxicillin 50mg/kg/p.o. The animals were treated every 6 hours. Each group was divided into three subgroups of five animals, which were killed after 6, 12 and 24 hours respectively. Five animals of the Group 1 were also killed at zero time, i.e., after the first administration of saline. Granulomas were removed and placed in test tubes, vortexed and the resulting suspension was spread on mannitol salt agar (SMA). After 18 hours, the microorganisms were counted manually. The results were compared by using Kruskal-Wallis test with a significance level of 5%. Chromatographic analysis showed that the two garlic species showed different chemical composition, but both presented organosulfur compounds, probably resulting from the allicin degradation. MIC and MBC of A. tuberosum showed no ability to inhibit or kill the S. aureus strain in any of the concentrations used. However, A. sativum showed MIC = 2mg/mL and MBC = 4mg/mL. The weight of the granulomas in the control group was lower (Kruskal- Wallis, p <0.05) than the other groups, considering each time separately. At times 12h and 24h, A. tuberosum showed bigger granulomatous-tissue weight than the other groups. It was observed that there was a decrease in the concentration of xi CFU/mL after 24 hours for all groups. Amoxicillin and 400mg/kg A. sativum reduced the S. aureus concentration after 12 hours. In general, all treatments caused significant reduction compared to the control group at all time periods. Furthermore, no statistically significant differences were observed regarding the number of bacteria recovered from the amoxicillin group in comparison to the other treatments at the 24 hours period. We conclude that the extracts were able to inhibit staphylococcal infection similarly to amoxicillin<br>Doutorado<br>Farmacologia, Anestesiologia e Terapeutica<br>Doutor em Odontologia
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Graziano, Talita Signoreti 1988. "Effects of statins in the bacterial viability and on biofilm of Staphylococcus aureus." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289491.
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Orientadores: Karina Cogo Müller, Francisco Carlos Groppo<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba<br>Made available in DSpace on 2018-08-25T11:18:29Z (GMT). No. of bitstreams: 1
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Previous issue date: 2014<br>Resumo: As estatinas são um grupo de fármacos que atuam como inibidores competitivos da enzima 3-Hidroxi-3-MetilGlutaril Coenzima-A Redutase (HMG-CoA redutase). Além de atuarem como importantes agentes hipolipemiantes, também apresentam outros efeitos, chamados de pleiotrópicos. Diversos estudos têm explorado um possível efeito protetor das estatinas atuando na redução na morbidade e mortalidade de várias doenças infecciosas. A atividade antimicrobiana das estatinas tem sido reportada por estudos in vivo e in vitro. O objetivo desse estudo foi avaliar os efeitos das estatinas sobre o crescimento e viabilidade de bactérias aeróbias patogênicas, e o efeito da sinvastatina sobre o biofilme de Staphylococcus aureus. Culturas das espécies de Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli e Enterococcus faecalis foram avaliadas na forma planctônica quanto à sensibilidade à atorvastatina, pravastatina e sinvastatina, através do teste de Concentração Inibitória Mínima (CIM). Além disso, diante da atividade apresentada pela sinvastatina contra S. aureus, foi determinada a ação dessa droga sobre a viabilidade celular através dos testes de Time-kill e Efeito pós-antibiótico (EPA). Também foi verificado um possível efeito sinérgico entre a sinvastatina e vancomicina. Por fim, a ação da sinvastatina foi avaliada contra biofilmes de S. aureus. Os valores de CIM da sinvastatina para o microrganismo S. aureus foram: 15,65 µg/ml (ATCC 29213) e 31,25 µg/ml (ATCC 33591, 43300, 14458 e 6538). A sinvastatina apresentou um perfil bacteriostático, e na concentração de 4xCIM seu EPA foi similar ao da vancomicina. Não foi encontrado nenhum tipo de interação entre a associação de sinvastatina e vancomicina. Entretanto, a sinvastatina foi capaz de reduzir a formação do biofilme nas concentrações entre 1/8CIM à 4xCIM. Além disso, na concentração 4xMIC foi capaz de diminuir a viabilidade, biomassa e a produção de polissacarídeos extracelulares e aumentar a produção de polissacarídeos intracelulares de biofilmes maduros de S. aureus. A produção de proteínas pelo biofilme não foi alterada. Em conclusão, os resultados encontrados mostram que a sinvastatina possui um grande potencial a ser explorado, principalmente em relação ao descobrimento de novos antimicrobianos<br>Abstract: Statins are drugs that competitively inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA). Besides their important lipid-lowering action, they also are pleiotropic agents. Several studies have explored a possible protective effect of statins to reduce the morbidity and mortality of various infectious diseases. The antimicrobial activity of statins has been reported by in vivo and in vitro studies. The aim of this study was to evaluate the effects of statins on the growth, viability and biofilm formation of pathogenic aerobic bacteria. The Minimum Inhibitory Concentrations (MIC) of atorvastatin, pravastatin and simvastatin against planktonic cells of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis strains were obtained. Since simvastatin showed activity against S. aureus, its effects on cell viability were evaluated in a time-kill and post-antibiotic effect (PAE) assays. A possible synergistic effect between simvastatin and vancomycin was also assessed. In addition, the effect of simvastatin against biofilms of S. aureus was tested. The MIC values of simvastatin for S. aureus were: 15.65 µg/ml (ATCC 29213) and 31.25 µg/ml (ATCC 33591, 43300, 14458 and 6538). Simvastatin showed a bacteriostatic profile, and in a 4x>MIC concentration the PAE was similar to vancomycin. No synergistic effect was found between simvastatin and vancomycin. Simvastatin was able to reduce the formation of biofilms in concentrations ranging from 1/8MIC to 4xMIC. In addition, the 4xMIC was able to decrease the viability, biomass and production of extracellular polysaccharides and increase the production of intracellular polysaccharides on mature biofilm of S. aureus. The protein production on biofilm was not altered in the presence of simvastatin . In conclusion, our results showed that simvastatin has a great potential to be explored, especially in relation to the development new antimicrobial agents<br>Mestrado<br>Farmacologia, Anestesiologia e Terapeutica<br>Mestra em Odontologia
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Cauz, Ana Carolina Guimarães 1987. "Avaliação da atividade da violaceína em linhagens de Staphylococcus aureus com hetero-resistência e resistência intermediária à vancomicina." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317033.
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Orientadores: Marcelo Brocchi, Bruna de Araújo Lima<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-27T10:37:08Z (GMT). No. of bitstreams: 1
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Previous issue date: 2015<br>Resumo: Isolados de Staphylococcus aureus correspondem a importantes patógenos para humanos e outros mamíferos, frequentemente associados a doenças em tecidos moles, tanto em infecções localizadas quanto sistêmicas. Tais infecções por S. aureus são geralmente de difícil tratamento devido à ocorrência de resistência antimicrobiana. Atualmente, linhagens de S. aureus resistentes à meticilina (MRSA) são isoladas em infecções e uma das últimas drogas de escolha para tratar essas doenças é a vancomicina, um anitbiótico glicopeptídeo. Entretanto, o isolamento de S. aureus com hetero-resistência e resistência intermediária à vancomicina (VISA e HVISA) tem sido descrito em diversos países. Dessa forma, a descoberta e caracterização de novas drogas para tratar infecções por S. aureus é uma necessidade urgente. Neste trabalho, há a descrição da atividade antimicrobiana da violaceína, uma molécula isolada de algumas espécies de bactérias ambientais, para linhagens VISA e hetero-VISA (HVISA) que se apresentaram resistentes a 24 antibióticos diferentes, o que indica um fenótipo de multirresistência (MRD). Os dados indicam uma atividade antimicrobiana expressiva da violaceína, sendo este efeito também observado através da realização de ensaios de efeito pós-antibiótico e curvas de tempo-morte. O efeito antimicrobiano da violaceína para linhagens de S. aureus resistentes a 24 antibióticos pertencentes a diferentes classes indicam um mecanismo distinto de ação da violaceína. Estes resultados sugerem a violaceína como uma droga em potencial para tratar infecções por S. aureus MRD, incluindo linhagens VISA e HVISA<br>Abstract: Staphylococcus aureus is an important pathogen to human and other mammals frequently associated with soft tissues, causing local and systemic infections. S. aureus infections are generally difficult to treat due to antimicrobial resistance. Nowadays, methicilin-resistant S. aureus (MRSA) strains are commonly isolated from infections and one of the last options to treat these diseases is vancomycin, a glycopeptide antibiotic. However, the isolation of vancomycin-intermediate or vancomycin-resistant S. aureus (VISA and VRSA strains) has been reported in different countries. Therefore, identification of new drugs to treat S. aureus infections is an urgent need. In this work, we described the antimicrobial activity of violacein, a molecule isolated from some groups of environmental bacteria, to VISA and hetero-VISA (HVISA) strains that are resistant to 24 different antimicrobials which indicates a multi-drug resistance (MDR) phenotype. Results reported here show a significant antibacterial activity of violacein. This effect was also observed in post antibiotic assays and in time-kill curves. The antibacterial effect of violacein to S. aureus strains resistant to a panel of 24 antimicrobial agents of different classes suggests a diverse antibacterial mechanism for violacein. These results suggest violacein as a potential drug to treat MDR S. aureus infections including VISA and HVISA strains<br>Mestrado<br>Microbiologia<br>Mestra em Genética e Biologia Molecular
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Royal, Maurice. "The effect of MV-II-065 on the phagocytosis of Staphylococcus aureus /." Connect to resource online, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1232132357.
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Blank, Tiana. "Comparative Mid-term Outcomes of Pediatric Hematogenous Methicillin-resistant Staphylococcus aureus and Methicillin-susceptible Staphylococcus aureus osteomyelitis." Thesis, The University of Arizona, 2018. http://hdl.handle.net/10150/626843.
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Lamers, Ryan Paul. "Evolutionary relationships among staphylococci and the prevention of Staphylococcus aureus nasal colonization." Doctoral diss., University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4782.
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Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that nasal carriage is a major vector for the transmission of virulent strains throughout the community. This hypothesis, however, has not been assessed in any great detail to identify the genetic relationships between clinical isolates of S. aureus and those strains being carried asymptomatically throughout the community. Also lacking within this field is a unified and robust estimate of phylogeny among species of Staphylococcus. Here, we report on a highly unified species phylogeny for Staphylococcus that has been derived using multilocus nucleotide data under multiple Bayesian and maximum likelihood approaches. Our findings are in general agreement with previous reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships. Regardless of methodology, strong nodal support and high topological agreement was observed with only minor variations in results between methods. Based on our phylogenetic estimates, we propose that Staphylococcus species can be evolutionarily clustered into 15 groups, and six species groups. In addition, our more defined phylogenetic analyses of S. aureus revealed strong genetic associations between both nasal carriage strains and clinical isolates. Genetic analyses of hypervariable regions from virulence genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates, but they also exhibited 100% sequence similarity within these regions. Our findings indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of infection and mortality. Due to nasal carriage of S. aureus being a risk factor for autoinfection, standardized preoperative decolonization has become a major consideration for the prevention of nosocomial infection. Toward this end, we have identified the macrocyclic ?-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibited bactericidal effects against S. aureus in both epithelium-free systems, and ex vivo models containing human airway epithelia. Importantly, RC-101 exhibited potent anti-S. aureus activities against all strains tested, including USA300. Moreover, RC-101 significantly reduced the adherence, survival, and proliferation of S. aureus on human airway epithelia without any noted cellular toxicity or the induction of a proinflammatory response. Collectively, our findings identify RC-101 as a potential preventative of S. aureus nasal colonization.<br>ID: 030646199; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (Ph.D.)--University of Central Florida, 2011.; Includes bibliographical references (p. 140-159).<br>Ph.D.<br>Doctorate<br>Molecular Biology and Microbiology<br>Medicine<br>Biomedical Sciences
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Raupelytė, Eglė. "Koaguliazei teigiamų stafilokokų išskyrimas iš gyvūnų augintinių." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140305_133815-68093.
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Darbo tikslas: nustatyti koaguliazei teigiamų stafilokokų paplitimą tarp gyvūnų augintinių.
Darbo uždaviniai:
1. išskirti koaguliazei teigiamus stafilokokus iš gyvūnų augintinių nosies ertmės;
2. išskirti koaguliazei teigiamus stafilokokus iš gyvūnų augintinių tiesiosios žarnos;
3. identifikuoti išskirtas stafilokokų padermes;
4. įvertinti įvairių veiksnių įtaką stafilokokų paplitimui;
5. nustatyti išskirtų stafilokokų atsparumą antimikrobinėms medžiagoms.
Darbo apimtis – 50 puslapių. Šiame darbe yra 6 lentelės bei 14 paveikslų. Magistro darbą sudaro 4 dalys. Pirmojoje dalyje apžvelgiami literatūros šaltiniai susiję su analizuojama tema, išskiriant koaguliazei teigiamų stafilokokų virulentiškumo veiksnius, atsparumą antimikrobinėms medžiagoms, sukeliamas ligas ir šių ligų gydymą. Aptariamas Staphylococcus aureus bei Staphylococcus pseudintermedius paplitimas ir paplitimą įtakojantys veiksniai. Antrojoje dalyje nurodyti tyrimo metodai, kuriais remiantis gauti duomenys tyrimų analizei. Trečiojoje dalyje analizuojami gauti tyrimo rezultatai pagal iškeltus uždavinius. Rezultatai pateikiami atsižvelgiant į statistinių duomenų patikimumą. Ketvirtoji dalis skirta literatūros apžvalgos ir tyrimo rezultatų skirtumų ir panašumų palyginimui.
Tyrimo metu iš gyvūnų augintinių nosies ertmės ir tiesiosios žarnos išskirti Staphylococcus aureus bei Staphylococcus pseudintermedius. Nustatyta, kad koaguliazei teigiamų stafilokokų paplitimas gyvūnų augintinių tarpe priklauso nuo gyvūnų... [toliau žr. visą tekstą]<br>The The goal of the study: to determine prevalence of coagulase positive staphylococci in companion animals.
The aim of the study:
1. to isolate coagulase positive staphylococci in nasal cavity of companion animals;
2. to isolate coagulase positive staphylococci in rectum of companion animals;
3. to identificate the isolated strains of staphylococci;
4. to evaluate risk factors for prevalence of staphylococci;
5. to determine antibiotic resistance in isolated staphylococci.
The master study consists of 50 pages. It includes 6 tables and 14 pictures. The master study consist of 4 major chapters. The first chapter is dedicated to review of literature that is related with analized topic. This part includes coagulase positive staphylococci virulence factors, antibiotic resistance, diseases caused by staphylococci and treatment use. Furthermore chapter contains review of the prevalence and risk factors influenced the prevalence of Staphylococcus aureus and Staphylococcus pseudintermedius. The second chapter introduce with materials and methods, that were used in the research at this master study. In the third chapter the results of the research are presented. The results are presented according to the statistical reliability. The fourth chapter is the resemblance and similarity comparision of the literature review and master study research.
In this master study Staphylococcus aureus and Staphylococcus pseudintermedius were isolated from nasal cavity and rectum of companion... [to full text]
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Harkins, Catriona P. "Genomic investigation into the evolution of Staphylococcus aureus and the micro-epidemiology of Staphylococcus aureus in atopic eczema." Thesis, University of Dundee, 2016. https://discovery.dundee.ac.uk/en/studentTheses/a762261b-a1ce-4511-bc48-89ca3197a635.
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Staphylococcus aureus is a highly adaptable organism, which has established itself as one the most important pathogens worldwide. It has co-evolved with humans adapting to life within the host as well as the interventions targeted to eradicate it. Despite its notoriety as a pathogen one of its natural habitats is as a commensal on the human skin. The overarching aim of this project was to understand the genetic basis of this organism's adaptation in the face of human intervention and influencing its survival in the human host, specifically during colonisation of the skin. From humankind's perspective arguably this organism's most significant adaptation is the development of drug resistance. Methicillin resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of the drug into clinical practice. Previous epidemiological and genetic evidence has always suggested that MRSA arose around this period, when the mecA gene encoding methicillin resistance carried on a Staphylococcal cassette chromosome mec (SCCmec) element, was acquired by S. aureus. In this work whole genome sequencing of a collection of the very first ever identified MRSA isolates was used to reconstruct the evolutionary events leading to the emergence of the archetypal MRSA lineage. This analysis revealed that S. aureus acquired the type I SCCmec element almost fourteen years prior to the first clinical use of methicillin, as a single horizontal event, and with its subsequent propagation leading to the genesis of MRSA. Staphylococcus aureus colonisation is a characteristic feature of the inflammatory skin disease atopic eczema (AE). In AE disease exacerbations are associated with an increased burden of this pathogen. Despite this the colonisation dynamics of S. aureus during disease flare eczema are poorly understood. Therefore the remainder of this body of work sought to genetically interrogate AE disease-associated S. aureus isolates to gain further understanding of how this organism contributes to the disease pathogenesis. Firstly by characterising genetic heterogeneity arising during colonisation in periods of disease flare in children with AE, in direct comparison to healthy children asymptomatically nasally colonised, looking for evidence of micro-evolutionary change suggestive of adaptation to the host. Secondly by comparing isolates from a cohort of AE cases to childhood nasal carriers to characterise the population structure and genetic content of AE disease vs. carriage isolates. These works demonstrated that colonisation in AE during disease flare is the result of a clonal expansion of a single strain type, mirroring the colonisation dynamics found in nasal carriers. In AE cases evidence of clinically relevant adaptive mutations were identified which were linked to prolonged periods of carriage, and included examples affecting global regulators of virulence and antimicrobial resistance. This analysis also revealed segregation in the genetic backgrounds of strains preferentially colonising AE skin in comparison to nasal epithelium, and evidence of the impact of prescribing practises between the disease populations.
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Weiß, Susanne. "Mortalität und Morbidität von chronischen Dialysepatienten bei Besiedlung mit Methicillin-sensiblem Staphylococcus aureus sowie Methicillin-resistentem Staphylococcus aureus." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-197315.
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Systemische Infektionen mit S. aureus (MSSA und MRSA) und Infektionen des Gefäßzugangs bei HD-Patienten sind eine der wichtigsten Ursachen für Morbidität und Mortalität in dieser speziellen Population. Infektionsrisikos stellen die zunehmende Verwendung von Fremdkörpern, wie Katheter und Graft als Gefäßzugänge, sowie die intensivmedizinische Behandlung bei älteren und multimorbiden Patienten dar. Unter den bakteriell bedingten Infektionen bleiben Staphylokokken der am häufigsten nachgewiesene Stamm. Mit dem zunehmenden Gebrauch von Vancomycin zur Behandlung von MSSA-Infektionen hat das Vorkommen von MRSA zugenommen. Dies macht die Entwicklung von alternativen Antibiotikaregimen nötig, die eine Selektion von MRSA-Spezies verhindern. Unter dieser Überlegung wurde auf die Behandlung mit Vancomycin bei Zugangs-bezogenen Infektionen verzichtet. Es wurde im Jahr 2000 durch ein Standardregime bestehend aus Flucloxacillin und Rifampicin ersetzt. Mithilfe eines Screeningprogramms wurde nach MSSA- (n=88) und MRSA- (n=1) Kolonisationen gesucht. Dies gelang mit Hilfe von Querschnitts-Screenings und Indikations-Screeninguntersuchungen bei Aufnahme über den Zeitraum von 2000 bis 2010.
Eine Besiedlung mit MRSA wurde bei nur einem Patienten während des 10-Jahres-Screenings registriert. Die gefundenen MSSA-Kolonisationen bei HD-Patienten beeinflussten die Morbidität und Mortalität nicht. Die Anzahl an HD-Patienten mit MSSA-Kolonisation nahm während des Beobachtungszeitraums von zehn Jahren ab
Behandlungen mit dem Vancomycin-freien Regime waren generell erfolgreich und resultierten in einem Rückgang der klinischen und laborativen Infektionsmarker und/oder negativen Blutkulturen.
Es konnte gezeigt werden, dass mit dem Gebrauch von vancomycinfreien Antibiotikaregimen ein erfolgreiches Management von Staphylokokkus-assoziierten Zugangsinfektionen bei HD-Patienten möglich ist.