Статті в журналах: "ST285"

1

Dargahi, Narges, John Matsoukas, and Vasso Apostolopoulos. "Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice." Brain Sciences 10, no. 2 (February 23, 2020): 126. http://dx.doi.org/10.3390/brainsci10020126.

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Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, probiotics have become prominent in recent years of investigation with regard to their health benefits. As such, in the current study, we determined the effects of Streptococcus thermophilus to agonist MBP83–99 peptide immunized mouse spleen cells. It was noted that Streptococcus thermophilus induced a significant increase in the expression of anti-inflammatory IL-4, IL-5, IL-10 cytokines, and decreased the secretion of pro-inflammatory IL-1β and IFN-γ. Regular consumption of Streptococcus thermophilus may therefore be beneficial in the management and treatment of autoimmune diseases such as multiple sclerosis.

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Athey, Taryn B. T., Katy Vaillancourt, Michel Frenette, Nahuel Fittipaldi, Marcelo Gottschalk, and Daniel Grenier. "Distribution of Suicin Gene Clusters in Streptococcus suis Serotype 2 Belonging to Sequence Types 25 and 28." BioMed Research International 2016 (2016): 1–7. http://dx.doi.org/10.1155/2016/6815894.

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Recently, we reported the purification and characterization of three distinct lantibiotics (named suicin 90-1330, suicin 3908, and suicin 65) produced by Streptococcus suis. In this study, we investigated the distribution of the three suicin lantibiotic gene clusters among serotype 2 S. suis strains belonging to sequence type (ST) 25 and ST28, the two dominant STs identified in North America. The genomes of 102 strains were interrogated for the presence of suicin gene clusters encoding suicins 90-1330, 3908, and 65. The gene cluster encoding suicin 65 was the most prevalent and mainly found among ST25 strains. In contrast, none of the genes related to suicin 90-1330 production were identified in 51 ST25 strains nor in 35/51 ST28 strains. However, the complete suicin 90-1330 gene cluster was found in ten ST28 strains, although some genes in the cluster were truncated in three of these isolates. The vast majority (101/102) of S. suis strains did not possess any of the genes encoding suicin 3908. In conclusion, this study indicates heterogeneous distribution of suicin genes in S. suis.

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Maaroufi, Raouaa, Olfa Dziri, Linda Hadjadj, Seydina M. Diene, Jean-Marc Rolain, and Chedly Chouchani. "Occurrence of NDM-1 and VIM-2 Co-Producing Escherichia coli and OprD Alteration in Pseudomonas aeruginosa Isolated from Hospital Environment Samples in Northwestern Tunisia." Diagnostics 11, no. 9 (September 4, 2021): 1617. http://dx.doi.org/10.3390/diagnostics11091617.

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Hospital environments constitute the main reservoir of multidrug-resistant bacteria. In this study we aimed to investigate the presence of Gram-negative bacteria in one Northwestern Tunisian hospital environment, and characterize the genes involved in bacterial resistance. A total of 152 environmental isolates were collected from various surfaces and isolated using MacConkey medium supplemented with cefotaxime or imipenem, with 81 fermenter bacteria (27 Escherichia coli, and 54 Enterobacter spp., including 46 Enterobacter cloacae), and 71 non-fermenting bacteria (69 Pseudomonas spp., including 54 Pseudomonas aeruginosa, and 2 Stenotrophomonas maltophilia) being identified by the MALDI-TOF-MS method. Antibiotic susceptibility testing was performed by disk diffusion method and E-Test was used to determine MICs for imipenem. Several genes implicated in beta-lactams resistance were characterized by PCR and sequencing. Carbapenem resistance was detected among 12 isolates; nine E. coli (blaNDM-1 (n = 8); blaNDM-1 + blaVIM-2 (n = 1)) and three P. aeruginosa were carbapenem-resistant by loss of OprD porin. The whole-genome sequencing of P. aeruginosa 97H was determined using Illumina MiSeq sequencer, typed ST285, and harbored blaOXA-494. Other genes were also detected, notably blaTEM (n = 23), blaCTX-M-1 (n = 10) and blaCTX-M-9 (n = 6). These new epidemiological data imposed new surveillance strategies and strict hygiene rules to decrease the spread of multidrug-resistant bacteria in this area.

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Schell, Celia M., Ana P. Tedim, Mercedes Rodríguez-Baños, Mónica D. Sparo, Sabina Lissarrague, Juan A. Basualdo та Teresa M. Coque. "Detection of β-Lactamase-Producing Enterococcus faecalis and Vancomycin-Resistant Enterococcus faecium Isolates in Human Invasive Infections in the Public Hospital of Tandil, Argentina". Pathogens 9, № 2 (20 лютого 2020): 142. http://dx.doi.org/10.3390/pathogens9020142.

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The study’s aim was to analyze the population structure of enterococci causing human invasive infections in a medium-sized Argentinian Hospital coincidental with a 5 year-period of increased recovery of antibiotic resistant enterococci (2010–2014). Species identification (biochemical testing/MALDI-TOF-MS), antimicrobial susceptibility (disk-diffusion) and clonal relatedness (PFGE/MLST/BAPS) were determined according to standard guidelines. β-lactamase production was determined by a nitrocefin test and confirmed by PCR/sequencing. The isolates were identified as Enterococcus faecalis and Enterococcus faecium at a 2:1 ratio. Most of the E. faecalis isolates, grouped in 25 PFGE-types (ST9/ST179/ST236/ST281/ST388/ST604/ST720), were resistant to high-levels (HLR) of gentamicin/streptomycin. A ST9 clone (bla+/HLR-gentamicin) was detected in patients of different wards during 2014. E. faecium isolates were grouped in 10 PFGE-types (ST25/ST18/ST19/ST52/ST792), with a low rate of ampicillin resistance. Five vancomycin-resistant E. faecium, three vanA (ST792/ST25) and two vanB (ST25) were detected. The ST25 clone carried either vanA or vanB. The recovery of a bla+-ST9-E. faecalis clone similar to that described in the late 1980s in Argentina suggests the possibility of a local hidden reservoir. These results reflect the relevance of local epidemiology in understanding the population structure of enterococci as well as the emergence and spread of antimicrobial resistance in predominant enterococcal clonal lineages.

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Maloney, Jenny G., and Monica Santin. "Mind the Gap: New Full-Length Sequences of Blastocystis Subtypes Generated via Oxford Nanopore Minion Sequencing Allow for Comparisons between Full-Length and Partial Sequences of the Small Subunit of the Ribosomal RNA Gene." Microorganisms 9, no. 5 (May 5, 2021): 997. http://dx.doi.org/10.3390/microorganisms9050997.

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Blastocystis is a common food- and water-borne intestinal protist parasite of humans and many other animals. Blastocystis comprises multiple subtypes (STs) based on variability within the small subunit ribosomal (SSU rRNA) RNA gene. Though full-length reference sequences of the SSU rRNA gene are a current requirement to name a novel Blastocystis subtype, full-length reference sequences are not currently available for all subtypes. In the present study, Oxford Nanopore MinION long-read sequencing was employed to generate full-length SSU rRNA sequences for seven new Blastocystis subtypes for which no full-length references currently exist: ST21, ST23, ST24, ST25, ST26, ST27, and ST28. Phylogenetic analyses and pairwise distance matrixes were used to compare full-length and partial sequences of the two regions that are most commonly used for subtyping. Analyses included Blastocystis nucleotide sequences obtained in this study (ST21 and ST23–ST28) and existing subtypes for which full-length reference sequences were available (ST1–ST17 and ST29). The relationships and sequence variance between new and existing subtypes observed in analyses of different portions of the SSU rRNA gene are discussed. The full-length SSU rRNA reference sequences generated in this study provide essential new data to study and understand the relationships between the genetic complexity of Blastocystis and its host specificity, pathogenicity, and epidemiology.

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Kakita, Tetsuya, Hisako Kyan, Masato Miyahira, Taketoshi Takara, Eri Nakama, Yumani Kuba, Takashi Kato, Minoru Nidaira, Jun Kudaka, and Nobuo Koizumi. "Novel genotypes of Leptospira interrogans serogroup Sejroe isolated from human patients in Okinawa Prefecture, Japan." Journal of Medical Microbiology 69, no. 4 (April 1, 2020): 587–90. http://dx.doi.org/10.1099/jmm.0.001169.

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Leptospirosis is a zoonotic disease caused by pathogenic spirochetes of Leptospira species. It is a public health issue in the tropics, including Okinawa, the southernmost prefecture of Japan. This study reports the first isolation of L. interrogans serogroup Sejroe from two human patients in Japan, and describes its molecular characterization using multilocus sequence typing (MLST) and multiple-locus variable-number tandem repeat analysis (MLVA). MLST on the two isolates, 168036 and 178129, showed that pfkB in 178129 is a novel allele, and that both isolates constitute novel sequence types (STs); ST286 for 168036 and ST287 for 178129. A minimum spanning tree based on seven alleles of L. interrogans indicates that both isolates are genetically close, but are distinct from known L. interrogans serogroup Sejroe strains. MLVA using 11 loci demonstrated that seven of the 11 loci were identical between the two isolates, whereas the identity between the isolates and the seven reference strains of L. interrogans serogroup Sejroe was zero to three loci. These results indicate that the isolates investigated in this study have novel genotypes, and are genetically closest to each other among the known L. interrogans serogroup Sejroe strains.

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Xu, Xinmin, Pengcheng Du, Huizhu Wang, Xiaoling Yang, Tingting Liu, Yuanyuan Zhang, and Yajie Wang. "Clinical characteristics, Cryptococcus neoformans genotypes, antifungal susceptibility, and outcomes in human immunodeficiency virus-positive patients in Beijing, China." Journal of International Medical Research 49, no. 5 (May 2021): 030006052110161. http://dx.doi.org/10.1177/03000605211016197.

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Cryptococcus neoformans is an environmental fungal pathogen that causes opportunistic infections and severe disseminated meningoencephalitis, mainly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS). In this study, the clinical characteristics, treatment protocols, and outcomes of 70 patients with AIDS and Cryptococcus neoformans infection at Beijing Ditan Hospital were retrospectively analyzed. We performed antimicrobial sensitivity tests and multilocus sequence typing (MLST) on C. neoformans isolates from these patients. The most common symptoms were headache (58.6%), fever (54.3%), and high cerebrospinal fluid pressure (≥200 mm H2O) (71.4%). All patients were positive for C. neoformans antigen in blood or cerebrospinal fluid. The CD4 cell counts of 92.8% (65/70) of patients were <100 cells/µL. In total, 74 C. neoformans isolates were obtained from the 70 patients. The 65 isolates that could be typed fell into 12 sequence types (STs) by MLST: ST5, ST31, ST63, ST202, ST237, ST289, ST295, ST296, ST298, ST324, ST337, and ST359. ST5 was the major type, accounting for 78.5% of isolates (51/65). This study comprehensively assessed the clinical and molecular epidemiology of C. neoformans in patients with AIDS and may inform the development of targeted prevention and treatment strategies for immunocompromised patients with C. neoformans infection.

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8

Shin, Se Ra, Seong Mi Noh, Woo Kyung Jung, Sook Shin, Young Kyung Park, Dong Chan Moon, Suk-Kyung Lim, Yong Ho Park та Kun Taek Park. "Characterization of Extended-Spectrum β-Lactamase-Producing and AmpC β-Lactamase-Producing Enterobacterales Isolated from Companion Animals in Korea". Antibiotics 10, № 3 (3 березня 2021): 249. http://dx.doi.org/10.3390/antibiotics10030249.

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The emergence of extended-spectrum cephalosporin (ESC)-resistant Gram-negative bacteria is of great concern in both human and veterinary medicine. The aim of this study was to investigate ESC-resistant bacterial isolates from companion animals in South Korea between 2017 and 2019. Isolates with ESC resistance genes, which were identified by PCR, were assessed for genetic relatedness by multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). In total, 91 ESC-resistant Escherichia coli, Klebsiella spp., Serratia spp., and Enterobacter cloacae isolates harbored the blaTEM gene. Among other ESC resistance genes, blaCTX-M-15, blaCIT, and blaCTX-M-55 were predominantly detected in E. coli isolates, whereas blaSHV and blaDHA were more frequently detected in Klebsiella pneumoniae isolates. In addition, all blaEBC-positive isolates were classified as E. cloacae. From the MLST results, blaCTX-M-9-carrying ST131, blaCIT-carrying ST405, and blaCTX-M-1-carrying ST3285 strains were dominant among E. coli isolates. ST273 and ST275 strains harboring blaSHV were frequently detected in K. pneumoniae isolates. Various sequence types were obtained in E. cloacae and Klebsiella oxytoca isolates. All isolates demonstrated unique PFGE profiles (<57–98% similarity) and were unlikely to be derived from a single clone. The present study reveals the presence and wide genetic distribution of ESC-resistant bacterial species in South Korean companion animals.

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Unlu, Ozge, Berken Rabun Ersoz, Ayse Istanbullu Tosun, and Mehmet Demirci. "Epidemic Klebsiella pneumoniae ST258 incidence in ICU patients admitted to a university hospital in Istanbul." Journal of Infection in Developing Countries 15, no. 05 (May 31, 2021): 665–71. http://dx.doi.org/10.3855/jidc.13430.

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Introduction: Klebsiella pneumoniae sequence type 258 (ST258) strains are globally distributed multi-drug resistant pathogens and can spread rapidly throughout the world, causing severe healthcare-associated invasive infections with limited antimicrobial treatment options. The aim of this study was to reveal the incidence of Klebsiella pneumoniae ST258 strains among the intensive care unit patients in a university hospital in Istanbul. Methodology: Consecutive nonreplicated 83 K. pneumoniae strains were isolated from various clinical samples of intensive care unit patients admitted to a university hospital in Istanbul, between November 2016 to December 2018. Bacterial identifications were performed via VITEK2. Antimicrobial susceptibility tests were conducted with Kirby Bauer’s disc diffusion test except for colistin which was performed with broth microdilution. Real-time PCR method was utilized in order to reveal ST258 positivity among the strains. Results: Antimicrobial susceptibility results revealed that 56 (67%) K. pneumoniae strains were carbapenem-resistant. Real-time PCR results demonstrated that 15 out of 83 (18%) K.pneumoniae strain were ST258. According to antimicrobial susceptibility test results of ST258 strains, 8 were found as carbapenem-resistant whereas 7 were found as carbapenem susceptible. 3 out of 8 (37.5%) carbapenem-resistant ST258 strains were found as resistant against all antibiotics tested. Conclusions: Our study revealed that K. pneumoniae ST258 which caused severe infections worldwide so far has also spread to Istanbul. We believe that rapid molecular methods for monitorization of these clones are useful. our results showed that ST258 is not linked to a multi-resistant strain and suggested that it does not contribute to multi-resistance formation alone.

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Shiratori, Erika, Mai Itoh, Mika Ohtaka, Shohei Nogami, and Shuji Tohda. "Mechanisms of Suppressive Effects of MYD88 Inhibitors on the Growth of Lymphoma and Leukemia Cells." Blood 128, no. 22 (December 2, 2016): 2773. http://dx.doi.org/10.1182/blood.v128.22.2773.2773.

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Abstract Introduction : Myeloid differentiation primary response gene 88 (MYD88) is an adaptor protein that binds to the Toll-like/interleukin-1 receptor to form a homodimer and activates NF-kB pathway. Activating MYD88 mutations are found in 90% of lymphoplasmacytic lymphoma (Waldenström's macroglobulinemia) cases and 30% of activated B-cell type diffuse large B-cell lymphoma (DLBCL) cases. To investigate the role of MYD88 in the growth of lymphoma/leukemia cells, with or without MYD88mutations, and to examine whether MYD88 inhibitors can be used as novel molecular-targeted drugs, we studied their effects on the growth of lymphoma and leukemia cells in vitro. Methods : Seven lymphoma/leukemia cell lines (TMD8 derived from DLBCL with MYD88 mutations, Daudi from Burkitt lymphoma, NALM-6 from B-ALL, Jurkat and KOPT-K1 from T-ALL, THP-1 and TMD7 from AML without MYD88 mutations) and normal lymphocytes from healthy volunteers were obtained, following an informed consent. The effect of the MYD88 inhibitor, ST2825, on the in vitro growth of these cell lines was then examined using the WST-8 colorimetric assay. ST2825 is a synthetic peptide-mimetic compound, which inhibits MYD88 dimerization. A Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, was used as the reference inhibitor. The effect of ST2825 on protein expression was examined by immunoblot analysis. Cell cycle analysis and Annexin V apoptosis assay were performed using flow cytometry. To comprehensively screen the changes in mRNA expression after ST2825 treatment, microarray analysis was performed for TMD8 and Jurkat cells. MYD88knockdown experiments using small interfering RNA were also performed. Results : The MYD88 protein was expressed in all cell lines. ST2825 (30 μM) suppressed the growth of all lymphoma/leukemia cell lines, but did not affect the viability of normal lymphocytes. The IC50 for TMD8 cells was similar to that for other cells, such as Daudi cells. Apoptosis assay revealed that ST2825 induces apoptosis in all the cell lines studied. In Daudi cells, ST2825 induced G2/M cell cycle arrest. Immunoblot analysis revealed that ST2825 suppresses the phosphorylation of certain NF-kB signaling components, such as RELA and IkB, in all cell lines. In TMD8, Daudi, and NALM-6 cells, ST2825 suppressed the phosphorylation of BTK, and MYD88 knockdown suppressed the phosphorylation of RELA and BTK. Microarray analysis revealed that ST2825 treatment downregulates the expression of various genes including MYD88, and upregulates the expression of other genes such as NGFR, FOSB, and HSP. Treatment with ibrutinib (1 nM) suppressed the growth of only TMD8 cells. Treatment with ST2825 plus ibrutinib additively suppressed the growth of TMD8 cells. Conclusions : The MYD88 inhibitor ST2825 suppresses the growth of various lymphoma and leukemia cells, suggesting that MYD88 is involved in regulating the growth of these cells; however, the off-target effects of ST2825 should be considered. Further investigation is required to assess the potential of MYD88 inhibitors as novel molecular-targeted drugs against lymphoma and leukemia. Disclosures No relevant conflicts of interest to declare.

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Thirapanmethee, Krit, Thayapa Srisiri-a-nun, Jantana Houngsaitong, Preecha Montakantikul, Piyatip Khuntayaporn та Mullika Chomnawang. "Prevalence of OXA-Type β-Lactamase Genes among Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates in Thailand". Antibiotics 9, № 12 (3 грудня 2020): 864. http://dx.doi.org/10.3390/antibiotics9120864.

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Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical health concern for the treatment of infectious diseases. The aim of this study was to investigate the molecular epidemiology of CRAB emphasizing the presence of oxacillinase (OXA)-type β-lactamase-encoding genes, one of the most important carbapenem resistance mechanisms. In this study, a total of 183 non-repetitive CRAB isolates collected from 11 tertiary care hospitals across Thailand were investigated. As a result, the blaoxa-51-like gene, an intrinsic enzyme marker, was detected in all clinical isolates. The blaoxa-23-like gene was presented in the majority of isolates (68.31%). In contrast, the prevalence rates of blaoxa-40/24-like and blaoxa-58-like gene occurrences in CRAB isolates were only 4.92% and 1.09%, respectively. All isolates were resistant to carbapenems, with 100% resistance to imipenem, followed by meropenem (98.91%) and doripenem (94.54%). Most isolates showed high resistance rates to ciprofloxacin (97.81%), ceftazidime (96.72%), gentamicin (91.26%), and amikacin (80.87%). Interestingly, colistin was found to be a potential drug of choice due to the high susceptibility of the tested isolates to this antimicrobial (87.98%). Most CRAB isolates in Thailand were of ST2 lineage, but some belonged to ST25, ST98, ST129, ST164, ST215, ST338, and ST745. Further studies to monitor the spread of carbapenem-resistant OXA-type β-lactamase genes from A. baumannii in hospital settings are warranted.

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Ogita, Tasuku, Megumi Nakashima, Hidetoshi Morita, Yasuo Saito, Takuya Suzuki, and Soichi Tanabe. "Streptococcus thermophilusST28 Ameliorates Colitis in Mice Partially by Suppression of Inflammatory Th17 Cells." Journal of Biomedicine and Biotechnology 2011 (2011): 1–9. http://dx.doi.org/10.1155/2011/378417.

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The effects ofStreptococcus thermophilusST28 on cytokine production by murine splenocytes stimulated with transforming growth factor-βplus interleukin- (IL-) 6 were evaluated. The addition of ST28 significantly repressed IL-17 production compared to ATCC 19258 (type strain). ST28 also decreased the number of Th17 cells in the stimulated splenocytes. The anti-inflammatory effects of ST28 administration were evaluated in mice with colitis induced by dextran sodium sulphate (DSS). Oral treatment of mice with ST28 ameliorated the intestinal lesions by DSS. Upon DSS treatment, IL-17 production in lamina propria lymphocytes (LPLs) was induced, but ST28 significantly decreased its production. ST28 also decreased the percentage of Th17 cells in LPL from DSS-induced colitis. The present results imply that ST28 suppresses the Th17 response in inflamed intestines and would be useful in the treatment of Th17-mediated diseases, such as inflammatory bowel disease.

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13

Rusu, Cristian E., Christopher D. Fassnacht, Dominique Sluse, Stefan Hilbert, Kenneth C. Wong, Kuang-Han Huang, Sherry H. Suyu, et al. "H0LiCOW – III. Quantifying the effect of mass along the line of sight to the gravitational lens HE 0435−1223 through weighted galaxy counts★." Monthly Notices of the Royal Astronomical Society 467, no. 4 (February 22, 2017): 4220–42. http://dx.doi.org/10.1093/mnras/stx285.

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Biehl, D., J. Heinze, and W. Winter. "Expected neutrino fluence from short Gamma-Ray Burst 170817A and off-axis angle constraints." Monthly Notices of the Royal Astronomical Society 476, no. 1 (February 2, 2018): 1191–97. http://dx.doi.org/10.1093/mnras/sty285.

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Long, R. J., Shude Mao, Juntai Shen, and Yougang Wang. "Made-to-measure galaxy models – III. Modelling with Milky Way observations." Monthly Notices of the Royal Astronomical Society 428, no. 4 (November 22, 2012): 3478–86. http://dx.doi.org/10.1093/mnras/sts285.

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Belloni, T. M., and D. Altamirano. "Discovery of a 34 Hz quasi-periodic oscillation in the X-ray emission of GRS 1915+105." Monthly Notices of the Royal Astronomical Society 432, no. 1 (April 13, 2013): 19–22. http://dx.doi.org/10.1093/mnras/stt285.

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Bonamente, M., J. Nevalainen, E. Tilton, J. Liivamägi, E. Tempel, P. Heinämäki, and T. Fang. "A possibleChandraandHubble Space Telescopedetection of extragalactic WHIM towards PG 1116+215." Monthly Notices of the Royal Astronomical Society 457, no. 4 (February 8, 2016): 4236–47. http://dx.doi.org/10.1093/mnras/stw285.

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Wang, Peng, Quan Guo, Noam I. Libeskind, Elmo Tempel, Chengliang Wei, and Xi Kang. "The shape alignment of satellite galaxies in Local Group-like pairs from the SDSS." Monthly Notices of the Royal Astronomical Society 484, no. 3 (January 28, 2019): 4325–36. http://dx.doi.org/10.1093/mnras/stz285.

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Bowden, A., V. Belokurov, and N. W. Evans. "Dipping our toes in the water: first models of GD-1 as a stream." Monthly Notices of the Royal Astronomical Society 449, no. 2 (March 24, 2015): 1391–400. http://dx.doi.org/10.1093/mnras/stv285.

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Milosavljevi , M., and V. Bromm. "Dwarf spheroidal satellite formation in a reionized Local Group." Monthly Notices of the Royal Astronomical Society 440, no. 1 (March 7, 2014): 50–67. http://dx.doi.org/10.1093/mnras/stu285.

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Adler, Robert, John Ewing, and Peter Taylor. "Citation Statistics." Statistical Science 24, no. 1 (February 2009): 1–14. http://dx.doi.org/10.1214/09-sts285.

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Kitahara, Maki, Sayaka Tsuchida, Koh Kawasumi, Hiromi Amao, Mitsuo Sakamoto, Yoshimi Benno, and Moriya Ohkuma. "Bacteroides chinchillae sp. nov. and Bacteroides rodentium sp. nov., isolated from chinchilla (Chinchilla lanigera) faeces." International Journal of Systematic and Evolutionary Microbiology 61, no. 4 (April 1, 2011): 877–81. http://dx.doi.org/10.1099/ijs.0.024026-0.

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Gram-negative anaerobic rods were isolated from chinchilla (Chinchilla lanigera) faeces and three strains, ST170T, ST180 and ST28T, were investigated taxonomically. On the basis of phylogenetic analyses and specific phenotypic characteristics, the three strains belonged to the genus Bacteroides. Phylogenetic analysis of their 16S rRNA gene sequences revealed that strains ST170T and ST180 formed a single cluster and a distinct line of descent. Strain ST170T exhibited 99.7 % 16S rRNA gene sequence similarity with strain ST180 and 95.1, 94.6 and 94.4 % 16S rRNA gene sequence similarity with Bacteroides massiliensis JCM 13223T, Bacteroides dorei JCM 13471T and Bacteroides vulgatus JCM 5826T, respectively. Strain ST28T also formed a distinct line of descent and exhibited the highest 16S rRNA gene sequence similarity with Bacteroides uniformis JCM 5828T (98.1 %). Low DNA–DNA relatedness (1 %) between strain ST28T and B. uniformis JCM 5828T clearly indicated that they belonged to different species. Analysis of hsp60 sequences also supported these relationships. The DNA G+C contents of strains ST170T and ST28T were 45.2 and 41.0 mol%, respectively. On the basis of phenotypic characteristics and phylogenetic data, two novel species, Bacteroides chinchillae sp. nov. (type strain ST170T = JCM 16497T = CCUG 59335T) and Bacteroides rodentium sp. nov. (type strain ST28T = JCM 16496T = CCUG 59334T), are proposed.

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Koreň, Ján, Michal Andrezál, Hana Drahovská, Zuzana Hubenáková, Adriána Liptáková, and Tibor Maliar. "Next-Generation Sequencing of Carbapenem-Resistant Klebsiella pneumoniae Strains Isolated from Patients Hospitalized in the University Hospital Facilities." Antibiotics 11, no. 11 (November 3, 2022): 1538. http://dx.doi.org/10.3390/antibiotics11111538.

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Carbapenem-resistant (CR) Klebsiella pneumoniae represents an urgent worldwide threat. We focused on CR K. pneumoniae in selected facilities of the University Hospital Bratislava (UHB) to investigate sequence types (STs), clonal relatedness, and antimicrobial resistance. Suspected carbapenem-nonsusceptible K. pneumoniae strains were obtained from hospitalized patients. Further examination included carbapenemase confirmation, cgMLST, and quantitative susceptibility testing. Of the total 41 CR K. pneumoniae strains, 26 (63.4%) were determined as ST11 in hospital No. 1; of these ST11, 22 (84.6%) were found in the first internal clinic. Six (14.6%) ST258 and three (7.3%) ST584 occurred in hospital No. 2; the most, i.e., four (66.7%), ST258 were detected in the geriatric clinic. In hospital No. 3, we found two (4.8%) ST584 and one (2.4%) ST258. Of the ST11 set, 24 (92.3%) produced NDM-1. Furthermore, seven (87.5) ST258 and five (100%) ST584 strains generated KPC-2. Antimicrobial resistance was as follows: ertapenem 97.6%, meropenem 63.4%, tigecycline 7.3%, eravacycline 7.3%, and colistin 2.5%. We revealed a presumably epidemiological association of ST11 with transmission, particularly in the first internal clinic of hospital No. 1, while ST258 and ST584 were related to interhospital dissemination between medical facilities No. 2 and No. 3. It is essential to prevent the circulation of these pathogens within and between healthcare facilities.

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Wang, Xiaomei, Shuang Zhou, Wei Yao, Hua Wan, Huangan Wu, Luyi Wu, Huirong Liu, Xuegui Hua, and Peifeng Shi. "Effects of Moxibustion Stimulation on the Intensity of Infrared Radiation of Tianshu (ST25) Acupoints in Rats with Ulcerative Colitis." Evidence-Based Complementary and Alternative Medicine 2012 (2012): 1–13. http://dx.doi.org/10.1155/2012/704584.

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ST25 is a key acupoint used in the treatment of ulcerative colitis by moxibustion stimulation, but the biophysical mechanism underlying its effects is still unknown. The aim of the present study was to explore the biophysical properties of ST25 acupoint stimulated by moxibustion in a rat model of ulcerative colitis. The infrared radiation intensity of fourteen wavelengths of ST25 showed significant differences between the normal and model control groups. The intensity of infrared radiation of forty wavelengths showed significant differences compared with the corresponding control points in normal rats. The intensity of infrared radiation of twenty-eight wavelengths showed significant differences compared with the corresponding control points in model rats. The intensity of infrared radiation of nine wavelengths in the herb-partition moxibustion group, eighteen wavelengths in the ginger-partition moxibustion group, seventeen wavelengths in the garlic-partition moxibustion group, and fourteen wavelengths in the warming moxibustion group of the left ST25 showed significant differences compared with that of the model control group. For the right-hand-side ST25, these values were 33, 33, 2, and 8 wavelengths, respectively. This indicated that one possible biophysical mechanism of moxibustion on ST25 in ulcerative colitis model rats might involve changes in the intensity of infrared radiation of ST25 at different wavelengths.

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Gomez-Simmonds, Angela, Michelle Greenman, Sean B. Sullivan, Joshua P. Tanner, Madeleine G. Sowash, Susan Whittier, and Anne-Catrin Uhlemann. "Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates." Journal of Clinical Microbiology 53, no. 7 (April 15, 2015): 2060–67. http://dx.doi.org/10.1128/jcm.03455-14.

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Despite the growing importance of carbapenem-resistantKlebsiella pneumoniae(CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R)K. pneumoniae, and susceptibleK. pneumoniaeisolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of thewziandblaKPCgenes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. TheblaKPC-3gene (30%) was restricted to ST258/wzi154, whereasblaKPC-2(70%) was observed for severalwziallele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas theK. pneumoniaesusceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and thewzi154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.

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Hesse, Shayla, Natalia Malachowa, Adeline Porter, Brett Freedman, Scott Kobayashi, Sankar Adhya, and Frank DeLeo. "1952. Bacteriophage Treatment Improves Survival of Mice Infected with Carbapenem-Resistant Klebsiella pneumoniae." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S60. http://dx.doi.org/10.1093/ofid/ofz359.129.

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Abstract Background Bacteriophage (phage) therapy is being considered as a treatment option for patients with multi-drug-resistant bacterial infections. However, there is a dearth of controlled clinical data to support therapeutic phage efficacy. As a first step toward addressing this deficiency, we tested the ability of two well-characterized phages, alone and in combination, to kill carbapenem-resistant Klebsiella pneumoniae (ST258) in blood in vitro and rescue mice from lethal ST258 infection. Methods Wild-type C57BL/6J mice were infected with a lethal inoculum of ST258 by intra-peritoneal (IP) injection followed 1 hour later by IP administration of lytic phage P1, P2, or P1+P2 at a multiplicity of infection (MOI) estimated at 1. Survival of each group of mice was tracked for 10 days. In separate experiments, mice were sacrificed at 1 hour, 24 hours, and 48 hours post-phage treatment. Mouse blood and tissues were collected at each timepoint for enumeration of bacteria and phage, screening for phage resistance, and histopathology. Results ST258 survival in mouse blood in vitro was significantly less after 1 hour of incubation with P1 or P1+P2 (MOI 1) compared with the control group (no phage). Consistent with the in vitro data, none of the mice (0/15) in the control group (no phage) survived to 10 days post-infection, whereas 12/15, 14/15, and 15/15 mice survived in the P2, P1, and P1+P2-treated groups, respectively (P < 0.0001). Conclusion Prompt, systemic administration of lytic bacteriophages rescued mice from lethal ST258 infection. These data support the potential of phage therapy to effectively treat infections caused by ST258. It will be important to assess whether, for other phage-bacteria combinations, in vitro lysis in blood correlates with in vivo treatment efficacy and therefore may have predictive utility. Disclosures All Authors: No reported Disclosures.

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Pitout, Johann D. D., Patrice Nordmann, and Laurent Poirel. "Carbapenemase-Producing Klebsiella pneumoniae, a Key Pathogen Set for Global Nosocomial Dominance." Antimicrobial Agents and Chemotherapy 59, no. 10 (July 13, 2015): 5873–84. http://dx.doi.org/10.1128/aac.01019-15.

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ABSTRACTThe management of infections due toKlebsiella pneumoniaehas been complicated by the emergence of antimicrobial resistance, especially to carbapenems. Resistance to carbapenems inK. pneumoniaeinvolves multiple mechanisms, including the production of carbapenemases (e.g., KPC, NDM, VIM, OXA-48-like), as well as alterations in outer membrane permeability mediated by the loss of porins and the upregulation of efflux systems. The latter two mechanisms are often combined with high levels of other types of β-lactamases (e.g., AmpC).K. pneumoniaesequence type 258 (ST258) emerged during the early to mid-2000s as an important human pathogen and has spread extensively throughout the world. ST258 comprises two distinct lineages, namely, clades I and II, and it seems that ST258 is a hybrid clone that was created by a large recombination event between ST11 and ST442. Incompatibility group F plasmids withblaKPChave contributed significantly to the success of ST258. The optimal treatment of infections due to carbapenemase-producingK. pneumoniaeremains unknown. Some newer agents show promise for treating infections due to KPC producers; however, effective options for the treatment of NDM producers remain elusive.

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Zhang, Shan-Shan, Man Liu, Dong-Ni Liu, Yu-Fu Shang, Yue-Hua Wang та Guan-Hua Du. "ST2825, a Small Molecule Inhibitor of MyD88, Suppresses NF-κB Activation and the ROS/NLRP3/Cleaved Caspase-1 Signaling Pathway to Attenuate Lipopolysaccharide-Stimulated Neuroinflammation". Molecules 27, № 9 (6 травня 2022): 2990. http://dx.doi.org/10.3390/molecules27092990.

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Neuroinflammation characterized by microglia activation is the mechanism of the occurrence and development of various central nervous system diseases. ST2825, as a peptide-mimetic MyD88 homodimerization inhibitor, has been identified as crucial molecule with an anti-inflammatory role in several immune cells, especially microglia. The purpose of the study was to investigate the anti-neuroinflammatory effects and the possible mechanism of ST2825. Methods: Lipopolysaccharide (LPS) was used to stimulate neuroinflammation in male BALB/c mice and BV2 microglia cells. The NO level was determined by Griess Reagents. The levels of pro-inflammatory cytokines and chemokines were determined by ELISA. The expressions of inflammatory proteins were determined by real-time PCR and Western blotting analysis. The level of ROS was detected by DCFH-DA staining. Results: In vivo, the improved levels of LPS-induced pro-inflammatory factors, including TNF-α, IL-6, IL-1β, MCP-1 and ICAM-1 in the cortex and hippocampus, were reduced after ST2825 treatment. In vitro, the levels of LPS-induced pro-inflammatory factors, including NO, TNF-α, IL-6, IL-1β, MCP-1, iNOS, COX2 and ROS, were remarkably decreased after ST2825 treatment. Further research found that the mechanism of its anti-neuroinflammatory effects appeared to be associated with inhibition of NF-κB activation and down-regulation of the NLRP3/cleaved caspase-1 signaling pathway. Conclusions: The current findings provide new insights into the activity and molecular mechanism of ST2825 for the treatment of neuroinflammation.

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Papagiannitsis, Costas C., Aggeliki Verra, Vasiliki Galani, Stelios Xitsas, Ibrahim Bitar, Jaroslav Hrabak, and Efthymia Petinaki. "Unravelling the Features of Success of VIM-Producing ST111 and ST235 Pseudomonas aeruginosa in a Greek Hospital." Microorganisms 8, no. 12 (November 28, 2020): 1884. http://dx.doi.org/10.3390/microorganisms8121884.

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The objective of this study was to analyze the characteristics that contribute to the successful dissemination of VIM-producing Pseudomonas aeruginosa (P. aeruginosa), belonging to ST111 and ST235, in a Greek hospital. A total of 120 non-repetitive P. aeruginosa, which had meropenem minimal inhibitory concentrations (MICs) greater than 2 mg/L, were studied. VIM-encoding genes were amplified and sequenced within their integrons. Isolates were typed by multilocus sequence typing (MLST). Six VIM-producers, representative of different integron structures and sequence types (STs), were completely sequenced using Illumina platform. Sixty-one P. aeruginosa were confirmed to produce VIM-type carbapenemases. ST111 dominated (n = 34) among VIM-producers, while 15 VIM-producers belonged to ST235. The blaVIM-like genes were located in three integron types, including In59, In595 and In1760, which were integrated into P. aeruginosa chromosomes. Whole genome sequencing (WGS) data demonstrated that ST111 and ST235 MBL producers carried several resistance and virulence genes. Additionally, the presence of type I-C and type I-E clustered regularly interspaced short palindromic repeats (CRISPR)/Cas locus was observed in ST235 and ST395 isolates, respectively. In conclusion, our findings confirmed the clonal spread of ST111 P. aeruginosa, carrying the VIM-2-encoding integron In59, in the University Hospital of Larissa (UHL). In addition, they highlighted the important role of high-risk clones, ST111 and ST235, in the successful dissemination and establishment into hospital settings of clinically important pathogens carrying resistance determinants.

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Ramírez-Pérez, Sergio, Luis Alexis Hernández-Palma, Edith Oregon-Romero, Brian Uriel Anaya-Macías, Samuel García-Arellano, Guillermo González-Estevez та José Francisco Muñoz-Valle. "Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor". Molecules 25, № 18 (21 вересня 2020): 4322. http://dx.doi.org/10.3390/molecules25184322.

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The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.

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Hu, Wen-Long, Chih-Hao Chang, and Yu-Chiang Hung. "Clinical Observations on Laser Acupuncture in Simple Obesity Therapy." American Journal of Chinese Medicine 38, no. 05 (January 2010): 861–67. http://dx.doi.org/10.1142/s0192415x10008305.

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A previous study has shown that laser acupuncture is a useful healing method for the treatment of visceral postmenopausal obesity in combination with a low-calorie diet. We observe and evaluate the therapeutic effect of laser acupuncture in subjects of simple obesity with a non-restrictive diet protocol. Subjects included 73 women and 22 men with simple obesity and body mass indices ≥ 27 kg/m2. Daily energy intake recommendations for obese females and males were 1620.0 and 1894.2 kcal in average, respectively. The gallium aluminum arsenide Handylaser Trion was used to apply 0.25 J of energy to each of the following acupuncture points three times per week for four consecutive weeks: Stomach, Hunger, ST25, ST28, ST40, SP15, and CV9. The subjects' body weights and body mass indices were recorded before treatment, and four weeks after treatment, and the percent reduction in each parameter was calculated. Statistically significant reductions in body weight and body mass index were detected after four weeks of treatment. The mean reduction and mean percent reduction in body weight were 3.17 kg and 3.80% (p < 0.0001), respectively. The corresponding values for the body mass index were 1.22 kg/m2 and 3.78% (p < 0.0001), respectively. We concluded that laser acupuncture was found to exert a therapeutic effect on simple obesity by reducing both body weight and body mass index. Moreover, subjects showed good compliance with this comfortable and non-restrictive diet protocol.

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Zhu, Xianwei, Zhibin Liu, Wenmin Niu, Yuan Wang, Aimin Zhang, Hongyan Qu, Jing Zhou, Lu Bai, Yong Yang, and Jie Li. "Effects of Electroacupuncture at St25 and Bl25 in a Sennae-induced rat model of diarrhoea-predominant irritable bowel syndrome." Acupuncture in Medicine 35, no. 3 (June 2017): 216–23. http://dx.doi.org/10.1136/acupmed-2016-011180.

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Background Electroacupuncture (EA) may have a role in the treatment of diarrhoea symptoms. Serotonin (5-hydroxytryptamine, 5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal (GI) tract, which initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. In addition, according to the results of our previous report, EA stimulation mediates GI peristalsis by increasing expression of 5-HT and tryptophan hydroxylase (TPH). Aim To investigate the effect of EA at acupuncture points ST25 and BL25 in a rat model of diarrhoea. Methods A diarrhoea-predominant irritable bowel syndrome (IBS-D) model was induced by Folium Sennae in 24 rats, which remained untreated (n=6) or received EA at ST25 (n=6), BL25 (n=6) or the combination of ST25 and BL25 (n=6). A control group of healthy rats was also included (n=6). After treatment, changes in loose stool and small intestine transit rates, enterochromaffin (EC) cell number, expression of TPH, and faecal/colonic 5-HT contents were measured. Results Loose stool and small intestine transit rates, EC cell numbers, colonic TPH expression and faecal/colonic 5-HT content of IBS-D rats were significantly increased relative to controls (p<0.05) and all these parameters were improved by EA at ST25, BL25, or ST25 and BL25 in combination (all p<0.05 vs untreated IBS-D rats). Conclusions EA at ST25 and/or BL25 had a positive effect on objective markers of diarrhoea in a IBS-D rat model and induced changes in EC cell number, colonic TPH and 5-HT contents. The effects of EA stimulation at ST25/BL25 on IBS-D rats may be mediated by excitation of sympathetic nerves.

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Hao, Mingju, Jessica Schuyler, Haifang Zhang, Elena Shashkina, Hong Du, Derrick E. Fouts, Michael Satlin, Barry N. Kreiswirth, and Liang Chen. "Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains." Journal of Antimicrobial Chemotherapy 76, no. 8 (May 3, 2021): 2017–23. http://dx.doi.org/10.1093/jac/dkab131.

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Abstract Background Recent studies indicated that the monosubstituted deoxystreptamine aminoglycoside apramycin is a potent antibiotic against a wide range of MDR Gram-negative pathogens. Objectives To evaluate the in vitro activity of apramycin against carbapenem-resistant Klebsiella pneumoniae (CRKp) isolates from New York and New Jersey, and to explore mechanisms of apramycin resistance. Methods Apramycin MICs were determined by broth microdilution for 155 CRKp bloodstream isolates collected from 2013 to 2018. MLST STs, wzi capsular types and apramycin resistance gene aac(3’)-IV were examined by PCR and Sanger sequencing. Selected isolates were further characterized by conjugation experiments and WGS. Results Apramycin MIC50/90 values were 8 and >128 mg/L for CRKp isolates, which are much higher than previously reported. Twenty-four isolates (15.5%) were apramycin resistant (MIC ≥64 mg/L) and they were all from the K. pneumoniae ST258 background. The 24 apramycin-resistant K. pneumoniae ST258 strains belonged to six different capsular types and 91.7% of them harboured the apramycin resistance gene aac(3’)-IV. Sequencing analysis showed that different ST258 capsular type strains shared a common non-conjugative IncR plasmid, co-harbouring aac(3’)-IV and blaKPC. A novel IncR and IncX3 cointegrate plasmid, p59494-RX116.1, was also identified in an ST258 strain, demonstrating how apramycin resistance can be spread from a non-conjugative plasmid through cointegration. Conclusions We described a high apramycin resistance rate in clinical CRKp isolates in the New York/New Jersey region, mainly among the epidemic K. pneumoniae ST258 strains. The high resistance rate in an epidemic K. pneumoniae clone raises concern regarding the further optimization and development of apramycin and apramycin-like antibiotics.

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Chilam, Jeremiah, Silvia Argimon, Marilyn Limas, Melissa Masim, June Gayeta, Marietta Lagrada, Agnettah Olorosa, et al. "Genomic surveillance of Pseudomonas aeruginosa in the Philippines, 2013–2014." Western Pacific Surveillance and Response Journal 12, no. 2 (June 30, 2021): 4–18. http://dx.doi.org/10.5365/wpsar.2020.11.1.006.

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Pseudomonas aeruginosa is an opportunistic pathogen that often causes nosocomial infections resistant to treatment. Rates of antimicrobial resistance (AMR) are increasing, as are rates of multidrug-resistant (MDR) and possible extensively drug-resistant (XDR) infections. Our objective was to characterize the molecular epidemiology and AMR mechanisms of this pathogen. We sequenced the whole genome for each of 176 P. aeruginosa isolates collected in the Philippines in 2013–2014; derived the multilocus sequence type (MLST), presence of AMR determinants and relatedness between isolates; and determined concordance between phenotypic and genotypic resistance. Carbapenem resistance was associated with loss of function of the OprD porin and acquisition of the metallo-β-lactamase (MBL) gene blaVIM. Concordance between phenotypic and genotypic resistance was 93.27% overall for six antibiotics in three classes, but varied among minoglycosides. The population of P. aeruginosa was diverse, with clonal expansions of XDR genomes belonging to MLSTs ST235, ST244, ST309 and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, and of transfer between hospitals. Most of the ST235 genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the Philippines. In addition, long-read sequencing of one representative XDR ST235 isolate identified an integron carrying multiple resistance genes (including blaVIM-2), with differences in gene composition and synteny from the P. aeruginosa class 1 integrons described previously. The survey bridges the gap in genomic data from the Western Pacific Region and will be useful for ongoing surveillance; it also highlights the importance of curtailing the spread of ST235 within the Philippines.

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Xu, Yan, Hanying Xu, Xinna Wang, Hongjuan Wen, Huifang Guan, Fa Gao, Hang Xu, et al. "Network-Based Elaboration of the Efficacy of the Dachangshu (BL25) and Tianshu (ST25) Points in the Treatment of Functional Constipation in Children through Inflammation, Adipocytokine, or Leptin Pathways." Evidence-Based Complementary and Alternative Medicine 2022 (December 6, 2022): 1–13. http://dx.doi.org/10.1155/2022/5315927.

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Constipation commonly occurs during childhood, and more than 95% of cases are classified as functional constipation. If not effectively treated, 20% of patients with childhood constipation can continue to exhibit symptoms into adulthood, which seriously affects their mental health and quality of life. The main feature of acupuncture or acupoint stimulation, a special branch of traditional Chinese medicine, is the selection of different acupoints for different diseases, and many worthy guidelines have been established for matching acupoints. The back-shu and front-mu point combination adheres to an important acupoint compatibility law that has been used since its proposal 2,500 years ago but has not yet been verified by the modern evidence-based experiments. This study focused on the back-shu and front-mu point combination using the Dachangshu (BL25) and Tianshu (ST25) points as examples to explore possible research methods for network acupoint-based stimulation based on existing evidence and to elucidate the mechanisms induced by BL25 and ST25 in the treatment of functional constipation in children (FCC). The study found that BL25 and ST25 have 20 common targets, namely, AQP8, DRD2, VIP, TAC1, IL6R, TNF, FOS, KIT, CHAT, HTR3A, GAS8, SOD3, TRPV1, MPO, CALCA, IL1B, P2RX7, NPY2R, IL10RA, and TPH1, and these targets may provide a strategy for the combined usage of BL25 and ST25. In addition, BL25 and ST25 can affect FCC treatment through inflammation-relatedTh17-cell differentiation, the NF-kappa B signaling pathway, and the Toll-like receptor signaling pathway. Adipocytokines or leptin may also comprise the mechanism through which BL25 and ST25 regulate FCC. In addition, BL25 and ST25 regulate FCC through 13 core targets, namely, NFKBIA, RELA, TNF, IKBKB, IRAK1, TLR4, MYD88, TNFRSF1A, IL1R1, TLR2, IL1B, TRAF6, and TNFRSF1B. In short, this study provides new ideas and methods for studying the mechanism of acupuncture points.

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Chen, Liang, Kalyan D. Chavda, Jacqueline Findlay, Gisele Peirano, Katie Hopkins, Johann D. D. Pitout, Robert A. Bonomo, Neil Woodford, Frank R. DeLeo, and Barry N. Kreiswirth. "Multiplex PCR for Identification of Two Capsular Types in Epidemic KPC-Producing Klebsiella pneumoniae Sequence Type 258 Strains." Antimicrobial Agents and Chemotherapy 58, no. 7 (April 14, 2014): 4196–99. http://dx.doi.org/10.1128/aac.02673-14.

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ABSTRACTWe developed a multiplex PCR assay capable of identifying two capsular polysaccharide synthesis sequence types (sequence type 258 [ST258]cps-1andcps-2) in epidemicKlebsiella pneumoniaeST258 strains. The assay performed with excellent sensitivity (100%) and specificity (100%) for identifyingcpstypes in 60 ST258K. pneumoniaesequenced isolates. The screening of 419 ST258 clonal isolates revealed a significant association betweencpstype andK. pneumoniaecarbapenemase (KPC) variant:cps-1is largely associated with KPC-2, whilecps-2is primarily associated with KPC-3.

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Guzvinec, Marija, Radosław Izdebski, Iva Butic, Marko Jelic, Maja Abram, Iva Koscak, Anna Baraniak, Waleria Hryniewicz, Marek Gniadkowski, and Arjana Tambic Andrasevic. "Sequence Types 235, 111, and 132 Predominate among Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates in Croatia." Antimicrobial Agents and Chemotherapy 58, no. 10 (July 28, 2014): 6277–83. http://dx.doi.org/10.1128/aac.03116-14.

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ABSTRACTA population analysis of 103 multidrug-resistantPseudomonas aeruginosaisolates from Croatian hospitals was performed. Twelve sequence types (STs) were identified, with a predominance of international clones ST235 (serotype O11 [41%]), ST111 (serotype O12 [15%]), and ST132 (serotype O6 [11%]). Overexpression of the natural AmpC cephalosporinase was common (42%), but only a few ST235 or ST111 isolates produced VIM-1 or VIM-2 metallo-β-lactamases or PER-1 or GES-7 extended-spectrum β-lactamases.

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Hawken, Shawn, Mary Hayden, Karen Lolans, Rachel Yelin, Robert Weinstein, Michael Lin, and Evan Snitkin. "Cohorting KPC+ Klebsiella pneumoniae (KPC-Kp)–Positive Patients—A Genomic Exposé of Cross-Colonization Hazards." Infection Control & Hospital Epidemiology 41, S1 (October 2020): s172—s173. http://dx.doi.org/10.1017/ice.2020.701.

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Background: Long-term acute-care hospitals (LTACHs) are disproportionately burdened by multidrug-resistant organisms (MDROs) like KPC-Kp. Although cohorting KPC-Kp+ patients into rooms with other carriers can be an outbreak-control strategy and may protect negative patients from colonization, it is unclear whether cohorted patients are at unintended increased risk of cross colonization with additional KPC-Kp strains. Methods: Cohorting KPC-Kp+ patients at admission into rooms with other positive patients was part of a bundled intervention that reduced transmission in a high-prevalence LTACH. Rectal surveillance culturing for KPC-Kp was performed at the start of the study, upon admission, and biweekly thereafter, capturing 94% of patients. We evaluated whole-genome sequencing (WGS) evidence of acquisition of distinct KPC-Kp strains in a convenience sample of patients positive for KPC-Kp at study start or admission to identify plausible secondary KPC-Kp acquisitions. Results: WGS multilocus sequence type (MLST) strain variability was observed among the 452 isolates from the 254 patients colonized by KPC-Kp (Fig. 1). Among the 32 patients who were positive at the beginning of the study or admission and had a secondary isolate collected at a later date (median, 89 days apart, range, 2–310 days), 17 (53%) had secondary isolates differing by MLST from their admission isolate. Although 60% of the KPC-Kp in the study was ST258, there was substantial genomic variation within ST258 isolates from the same patient (range, 0–102 genetic variants), suggesting multiple acquisitions of distinct ST258 isolates. Among the 17 patients who imported ST258 and had ST258 isolated again later, 11 (65%) carried secondary isolates genetically closer to isolates from other importing patients than to their own ST258 (Fig. 2). Examination of spatiotemporal exposures among patients with evidence of multiple acquisitions revealed that 11 (65%) patients with multiple MLSTs shared a room with a patient who was colonized with an isolate matching the secondary MLST, and 6 (35%) patients who carried multiple distinct ST258 isolates shared a room with a patient who imported these closely related isolates prior to secondary acquisition. Conclusions: Half of patients who imported KPC-Kp and had multiple isolates available had genomically supported secondary acquisitions linked to roommates who carried the acquired strains. Although cohorting is intended to protect negative patients from acquiring MDROs, this practice may promote multiple strain acquisitions by colonized patients in the cohort, potentially prolonging the period of MDRO carriage and increasing time at risk of infection. Our findings add to the debate about single-patient rooms, which may be preferred to cohorts to minimize potential harms by reducing MDRO transmission.Funding: NoneDisclosures: None

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Nadarajah, Jeya, Mark J. S. Lee, Lisa Louie, Latha Jacob, Andrew E. Simor, Marie Louie, and Martin J. McGavin. "Identification of different clonal complexes and diverse amino acid substitutions in penicillin-binding protein 2 (PBP2) associated with borderline oxacillin resistance in Canadian Staphylococcus aureus isolates." Journal of Medical Microbiology 55, no. 12 (December 1, 2006): 1675–83. http://dx.doi.org/10.1099/jmm.0.46700-0.

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Borderline oxacillin-resistant Staphylococcus aureus (BORSA) exhibit oxacillin MIC values of 1–8 μg ml−1, but lack mecA, which encodes the low-affinity penicillin-binding protein (PBP)2a. The relationship of the BORSA phenotype with specific genetic backgrounds was assessed, as well as amino acid sequence variation in the normal PBP2. Among 38 BORSA, 26 had a common PFGE profile of genomic DNA, and were multilocus sequence type (ST)25. The other isolates were genetically diverse. Complete pbp2 sequences were determined for three BORSA, corresponding to ST25, ST1 and ST47, which were selected on the basis of lacking blaZ-encoded β-lactamase. The essential transpeptidase-domain-encoding segment of pbp2 was also sequenced from seven additional ST25 isolates. Amino acid substitutions occurred in the transpeptidase domain of all BORSA, irrespective of clonal type. A Gln629→Pro substitution was common to all ST25 BORSA, but most could be distinguished from one another by additional unique substitutions in the transpeptidase domain. The ST1 and ST47 isolates also possessed unique substitutions in the transpeptidase domain. Plasmid-mediated expression of pbp2 from an ST25 or ST1 isolate in S. aureus RN6390 increased its oxacillin MIC from 0.25 to 4 μg ml−1, while pbp2 from a susceptible strain, ATCC 25923, had no effect. Therefore, different amino acid substitutions in PBP2 of diverse BORSA lineages contribute to borderline resistance. The predominant ST25 lineage was not related to any of the five clonal complexes that contain meticillin-resistant S. aureus (MRSA), suggesting that ST25 cannot readily acquire mecA-mediated resistance.

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Zhu, Xianwei, Zhibin Liu, Yifei Qin, Wenmin Niu, Qiang Wang, Lu Li, and Jing Zhou. "Analgesic Effects of Electroacupuncture at St25 and Cv12 in a Rat Model of Postinflammatory Irritable Bowel Syndrome Visceral Pain." Acupuncture in Medicine 36, no. 4 (August 2018): 240–46. http://dx.doi.org/10.1136/acupmed-2016-011320.

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Background Treatment with electroacupuncture (EA) at ST25 and CV12 has a significant analgesic effect on postinflammatory irritable bowel syndrome (PI-IBS) visceral pain. Enterochromaffin (EC) cells and serotonin (5-hydroxytryptamine (5-HT)) are important in the development of visceral hyperalgesia. Objective To investigate the analgesic effect and underlying mechanisms of EA at ST25 and CV12 on the treatment of trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS visceral hyperalgesia in rats. Methods After EA at ST25 and CV12, changes in abdominal withdrawal reflex (AWR), electromyography (EMG) recordings, colonic EC cell numbers, and expression of tryptophan hydroxylase (TPH), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) of TNBS-induced PI-IBS visceral hyperalgesia in rats were examined. Results The results of AWR tests and EMG recordings indicated a significant analgesic effect of EA stimulation at ST25 and CV12on PI-IBS visceral hyperalgesia (p<0.05). In addition, the increased EC cell numbers and colonic expression of TPH and 5-HT in rats with TNBS-induced PI-IBS visceral hyperalgesia were significantly reduced by EA (p<0.05). Conclusions EA stimulation at ST25 and CV12 can attenuate visceral hyperalgesia. This analgesic effect may be mediated via reduction of both colonic EC cell number and 5-HT concentration.

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Tzouvelekis, L. S., V. Miriagou, S. D. Kotsakis, K. Spyridopoulou, E. Athanasiou, E. Karagouni, E. Tzelepi, and G. L. Daikos. "KPC-Producing, Multidrug-Resistant Klebsiella pneumoniae Sequence Type 258 as a Typical Opportunistic Pathogen." Antimicrobial Agents and Chemotherapy 57, no. 10 (July 15, 2013): 5144–46. http://dx.doi.org/10.1128/aac.01052-13.

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ABSTRACTThe virulence of a KPC-producingKlebsiella pneumoniaesequence type 258 (ST258) strain representing those circulating in Greece was assessed in a mouse septicemia model. The strain was virtually avirulent (50% lethal dose, >108and 5 × 107CFU for immunocompetent and neutropenic animals, respectively). Also, it was highly susceptible to serum killing, rapidly phagocytosedin vitro, and classified as K41, which is not among the virulent capsular types. The findings indirectly support the notion that high ST258-associated mortality is largely due to inefficient antimicrobial treatment.

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Andrade, Leonardo Neves, Tânia Curiao, Joseane Cristina Ferreira, Juliana Mucedola Longo, Eduardo Carneiro Clímaco, Roberto Martinez, Fernando Bellissimo-Rodrigues, et al. "Dissemination ofblaKPC-2by the Spread of Klebsiella pneumoniae Clonal Complex 258 Clones (ST258, ST11, ST437) and Plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae Species in Brazil." Antimicrobial Agents and Chemotherapy 55, no. 7 (May 16, 2011): 3579–83. http://dx.doi.org/10.1128/aac.01783-10.

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ABSTRACTThis article reports the spread ofblaKPC-2in the Sao Paulo and Rio de Janeiro states, facilitated by globally spreadK. pneumoniaeclonal complex 258 (CC258) clones (ST258, ST11, and ST437) and a diversity of plasmids (IncFII, IncN, and IncL/M, two untypeable plasmids carrying Tn4401a or Tn4401b) successfully disseminated among species of theEnterobacteriaceae(Enterobacter cloacae,Serratia marcescens, andCitrobacter freundii). It also constitutes the first description of sequence type 258 (ST258) in Brazil, which was associated with a nosocomial hospital outbreak in Ribeirao Preto city.

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Mathers, Amy J., Nicole Stoesser, Anna E. Sheppard, Louise Pankhurst, Adam Giess, Anthony J. Yeh, Xavier Didelot, et al. "Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae at a Single Institution: Insights into Endemicity from Whole-Genome Sequencing." Antimicrobial Agents and Chemotherapy 59, no. 3 (January 5, 2015): 1656–63. http://dx.doi.org/10.1128/aac.04292-14.

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ABSTRACTThe global emergence ofKlebsiella pneumoniaecarbapenemase-producingK. pneumoniae(KPC-Kp) multilocus sequence type ST258 is widely recognized. Less is known about the molecular and epidemiological details of non-ST258K. pneumoniaein the setting of an outbreak mediated by an endemic plasmid. We describe the interplay ofblaKPCplasmids andK. pneumoniaestrains and their relationship to the location of acquisition in a U.S. health care institution. Whole-genome sequencing (WGS) analysis was applied to KPC-Kpclinical isolates collected from a single institution over 5 years following the introduction ofblaKPCin August 2007, as well as two plasmid transformants. KPC-Kpfrom 37 patients yielded 16 distinct sequence types (STs). Two novel conjugativeblaKPCplasmids (pKPC_UVA01 and pKPC_UVA02), carried by the hospital index case, accounted for the presence ofblaKPCin 21/37 (57%) subsequent cases. Thirteen (35%) isolates represented an emergent lineage, ST941, which contained pKPC_UVA01 in 5/13 (38%) and pKPC_UVA02 in 6/13 (46%) cases. Seven (19%) isolates were the epidemic KPC-Kpstrain, ST258, mostly imported from elsewhere and not carrying pKPC_UVA01 or pKPC_UVA02. Using WGS-based analysis of clinical isolates and plasmid transformants, we demonstrate the unexpected dispersal ofblaKPCto many non-ST258 lineages in a hospital through spread of at least two novelblaKPCplasmids. In contrast, ST258 KPC-Kpwas imported into the institution on numerous occasions, with otherblaKPCplasmid vectors and without sustained transmission. Instead, a newly recognized KPC-Kpstrain, ST941, became associated with both novelblaKPCplasmids and spread locally, making it a future candidate for clinical persistence and dissemination.

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Kabic, Jovana, Gianuario Fortunato, Ivone Vaz-Moreira, Dusan Kekic, Milos Jovicevic, Jovan Pesovic, Lazar Ranin, Natasa Opavski, Célia M. Manaia та Ina Gajic. "Dissemination of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa in Serbian Hospital Settings: Expansion of ST235 and ST654 Clones". International Journal of Molecular Sciences 24, № 2 (12 січня 2023): 1519. http://dx.doi.org/10.3390/ijms24021519.

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This nationwide study aimed to investigate the molecular characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa in Serbia, underlying resistance mechanisms, the genetic context of detected MBL genes, and the clonal relationship between isolates harboring genes-encoding MBL. Overall, 320/5334 isolates collected from 2018 to 2021 were identified as P. aeruginosa. Carbapenem-resistant P. aeruginosa (CRPA) were screened for the presence of blaVIM, blaIMP, and blaNDM, genes whereas MBL-positive isolates were tested for the presence of the blaCTX-M-2, blaPER, blaTEM, blaSHV, blaVEB, and blaGES. Multilocus sequence typing and phylogenomic analysis were performed for P. aeruginosa-producing MBL. The majority of the P. aeruginosa isolates were recovered from the lower respiratory tract (n = 120; 37.5%) and wound specimens (n = 108; 33.75%). CRPA isolates accounted for 43.1% (n = 138) of the tested isolates, 31 out of them being blaNDM-1-positive (22.5%). The colistin resistance rate was 0.3%. MLST analysis revealed the occurrence of ST235 (n = 25) and ST654 (n = 6), mostly confined to Serbia. The distribution of beta-lactamase-encoding genes in these isolates suggested clonal dissemination and possible recombination: ST235/blaNDM-1, ST235/blaNDM-1/blaPER-1, ST654/blaNDM-1, ST654/blaNDM-1/blaPER-1, and ST654/blaNDM-1/blaGES-5. High-risk clones ST235 and ST654 identified for the first time in Serbia, are important vectors of acquired MBL and ESBL and their associated multidrug resistance phenotypes represent a cause for considerable concern.

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Shropshire, William C., An Q. Dinh, William R. Miller, Heather Ecklund, Audrey Wanger, Truc T. Tran, Cesar A. Arias, and Blake Hanson. "626. Mobile Genetic Element Dynamics of Co-Circulating Klebsiella pneumoniae Sequence Types Carrying blaKPC in Houston, Texas." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S290—S291. http://dx.doi.org/10.1093/ofid/ofz360.694.

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Abstract Background Carbapenem-resistant Klebsiella pneumoniae (CR-Kpn) are a significant cause of hospital-associated infections. Class A β-lactamases, e.g., Klebsiella pneumoniae carbapenemases (KPCs), are major contributors to carbapenem resistance. Sequence type 258 (ST258) is the most common genetic lineage of CR-Kpn associated with blaKPC carriage. Recently, a newly emergent lineage ST307 has been identified within the Houston metropolitan region. The transmission of blaKPC and other antimicrobial resistance (AMR) genes is driven largely by exchange of mobile genetic elements (MGEs). We sought to describe the dynamics of horizontal gene transfer (HGT) in particular between co-circulating strains of ST307 and ST258. Methods Long-read sequencing technologies allow us to resolve plasmid sequences and their associated AMR genes as well as characterize a comprehensive range of MGEs enabling transmission of these clinically important resistance mechanisms. CR-Kpn isolates were collected as part of a study to describe CRE burden within a Houston metropolitan hospital system. The Oxford Nanopore Technology (ONT) GridION X5 was used for long-read sequencing with Illumina short-read data used to refine and generate high-quality, consensus assemblies. A custom bioinformatic pipeline was used to resolve plasmid structures and identify the genomic context of plasmids carrying blaKPC variants. Results 95 Kpn isolates were collected from May to December 2017. Phylogenetic and in silico MLST analysis revealed 38/95 (40%) and 35/95 (37%) were ST258 and ST307, respectively. 86% of Kpn isolates carried one or more IncF-type conjugative plasmids, which were the prime vectors for blaKPC intercellular transmission. Interestingly, we found similar AMR-harboring plasmids within ST258 and ST307 composed of mosaic, modular IS26 and Tn3-like transposase mediated elements that carried multiple AMR determinants including blaKPC variants (Figure 1). Conclusion We were able to characterize mechanisms by which ST307 and ST258 lineages may transfer AMR determinants. There are clinically relevant implications to these HGT events that occur between these lineages as they may provide insights into how resistance differentially develops. Disclosures All authors: No reported disclosures.

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Thiry, Damien, Virginie Passet, Katarzyna Danis-Wlodarczyk, Cédric Lood, Jeroen Wagemans, Luisa De Sordi, Vera van Noort, et al. "New Bacteriophages against Emerging Lineages ST23 and ST258 of Klebsiella pneumoniae and Efficacy Assessment in Galleria mellonella Larvae." Viruses 11, no. 5 (May 3, 2019): 411. http://dx.doi.org/10.3390/v11050411.

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Klebsiella pneumoniae is a bacterial pathogen of high public health importance. Its polysaccharide capsule is highly variable but only a few capsular types are associated with emerging pathogenic sublineages. The aim of this work is to isolate and characterize new lytic bacteriophages and assess their potential to control infections by the ST23 and ST258 K. pneumoniae sublineages using a Galleria mellonella larvae model. Three selected bacteriophages, targeting lineages ST258 (bacteriophages vB_KpnP_KL106-ULIP47 and vB_KpnP_KL106-ULIP54) and ST23 (bacteriophage vB_KpnP_K1-ULIP33), display specificity for capsular types KL106 and K1, respectively. These podoviruses belong to the Autographivirinae subfamily and their genomes are devoid of lysogeny or toxin-associated genes. In a G. mellonella larvae model, a mortality rate of 70% was observed upon infection by K. pneumoniae ST258 and ST23. This number was reduced to 20% upon treatment with bacteriophages at a multiplicity of infection of 10. This work increases the number of characterized bacteriophages infecting K. pneumoniae and provides information regarding genome sequence and efficacy during preclinical phage therapy against two prominent sublineages of this bacterial species.

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Nguyen, Minh-Hong, Liang Chen, Shaoji Cheng, Kevin Squires, Binghua Hao, Ryan K. Shields, Barry Kreiswirth, and Cornelius J. Clancy. "246. Carbapenem-resistant Klebsiella (CRK) Bloodstream Infections (BSIs) Are Caused by Bacterial Populations That Are Genotypically and Phenotypically Diverse." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S138—S139. http://dx.doi.org/10.1093/ofid/ofz360.321.

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Abstract Background The majority of bacterial BSIs are believed to stem from a single, clonal organism. We hypothesized that most CRK BSIs are caused by genetically diverse, clonal strains that exhibit different phenotypes. Methods Blood cultures (BCs) that were positive for CRK from each of 10 patients (patients) were streaked onto agar plates, and 100 individual colonies were chosen for Illumina whole-genome sequencing. Strains from 3 patients were tested for in vitro phenotypes and virulence in mice. Results Patients had BSIs due to ST258 K. pneumoniae (Kp; 6), non-ST258 Kp (3), and K. michiganensis (Km; 1). 5 patients were infected with strains that differed by core genome single nucleotide polymorphism phylogeny (2–5 unique genotypes/patient) [figure]. 6 patients were infected with strains that differed by gene or plasmid content, and/or gene deletions [table]. Differences in individual patients encompassed antibiotic resistance and putative virulence genes (including mixtures of blaKPC+ and blaKPC– strains, and various capsular (CPS) and porin mutant strains). In total, BSIs in 8 of 10 patients were caused by a genotypically diverse population. In each of 3 patients, genotypically diverse ST258 Kp strains demonstrated significant differences in antibiotic susceptibility, CPS content, mucoviscosity, adherence, resistance to serum killing, and mortality rates and tissue burdens during BSIs of mice. ST258 strains from a pt with and without a KPC-bearing IncFIA plasmid differed in β-lactam susceptibility, but were equally virulent. Progressive loss of CPS in ST258 strains from another patient enhanced serum killing and adherence, and attenuated virulence. Using PCR markers to test 96 colonies per positive BC bottle, we demonstrated that strains selected by the clinical micro lab accounted for 2% to 98% of a population in different patients. Conclusion CRK causing BSIs in most patients demonstrated remarkable genotypic diversity, which impacted antibiotic susceptibility, virulence and other phenotypes. Differences were not recognized during hospitalization since clinical labs select single, morphologically distinct colonies for evaluation. Studies are needed to understand the clinical implications of our findings, diversity during other BSIs, and whether clinical lab practices need revision. Disclosures All authors: No reported disclosures.

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Bocharova, Yu A., T. A. Savinova, A. V. Lyamin, O. V. Kondratenko, S. V. Polikarpova, S. V. Zhilina, N. I. Fedorova, et al. "Genome features and antibiotic resistance of Pseudomonas aeruginosa strains isolated in patients with cystic fibrosis in the Russian Federation." Russian Clinical Laboratory Diagnostics 66, no. 10 (October 18, 2021): 629–34. http://dx.doi.org/10.51620/0869-2084-2021-66-10-629-634.

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Cystic fibrosis (CF) is a common genetic disease, manifested by airway obstruction and chronic respiratory infection. The most prevalent infectious agent in airways of CF patients is Pseudomonas aeruginosa. This study aimed to determine sequence-types, antimicrobial resistance phenotypes and genes defining adaptive antibiotic resistance in P. aeruginosa isolates recovered from CF patients in Russia. In total, 84 P. aeruginosa strains from 64 CF patients were analyzed. Susceptibility to antibiotics was determined by disk diffusion test. Whole-genome sequencing (WGS) was performed on MGISEQ-2000 platform. SPAdes software, Galaxy, ResFinder, PubMLST were used for analysis of WGS data. Examined P. aeruginosa isolates belonged to 53 different sequence-types (STs), including 6 new STs. High-risk epidemic clone ST235 (10%) and clonal CF P. aeruginosa strains ST17, ST242, ST274 (7%) were detected. Non-susceptibility to ticarcillin-clavulanate, cefepime, imipenem was observed in 63%, 12% and 25% of isolates, respectively; to tobramycin - in 24%, to amikacin - in 35%; to ciprofloxacin, levofloxacin - in 35% and 57% of strains, respectively. Multidrug-resistant phenotype was detected in 18% of isolates. In examined strains, genes of beta-lactamases VIM-2 (5 ST235 strains), VEB-1 (two ST2592 strains), GES-1 (1 ST235 strain), PER-1 (1 ST235 strain) were found. Ciprofloxacin-modifying enzyme CrpP gene was detected in 67% of isolates, aminoglycoside-modifying enzymes AAD, ANT, AAC genes - in 7%, 4%, 12% of strains, respectively. P. aeruginosa isolates from CF patients in Russia demonstrate a high clonal diversity, which is similar to other P. aeruginosa infections. The isolates of high-risk clone and clonal CF P. aeruginosa strains are detected.

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Iovleva, Alina, Roberta T. Mettus, Christi L. McElheny, Mustapha M. Mustapha, Daria Van Tyne, Ryan K. Shields, A. William Pasculle, Vaughn S. Cooper, and Yohei Doi. "Reduced ceftazidime and ertapenem susceptibility due to production of OXA-2 in Klebsiella pneumoniae ST258." Journal of Antimicrobial Chemotherapy 74, no. 8 (May 24, 2019): 2203–8. http://dx.doi.org/10.1093/jac/dkz183.

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Abstract Background OXA-2 is a class D β-lactamase that confers resistance to penicillins, as well as narrow-spectrum cephalosporins. OXA-2 was recently reported to also possess carbapenem-hydrolysing activity. Here, we describe a KPC-2-encoding Klebsiella pneumoniae isolate that demonstrated reduced susceptibility to ceftazidime and ertapenem due to production of OXA-2. Objectives To elucidate the role of OXA-2 production in reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 clinical isolate. Methods MICs were determined by the agar dilution method. WGS was conducted to identify and compare resistance genes between isolates. Expression of KPC-2 was quantified by quantitative RT–PCR and immunoblotting. OXA-2 was expressed in Escherichia coli TOP10, as well as in K. pneumoniae ATCC 13883, to define the relative contribution of OXA-2 in β-lactam resistance. Kinetic studies were conducted using purified OXA-2 enzyme. Results K. pneumoniae 1761 belonged to ST258 and carried both blaKPC-2 and blaOXA-2. However, expression of blaKPC-2 was substantially reduced due to an IS1294 insertion in the promoter region. K. pneumoniae 1761, K. pneumoniae ATCC 13883 and E. coli TOP10 carrying blaOXA-2-harbouring plasmids showed reduced susceptibility to ertapenem and ceftazidime, but meropenem, imipenem and cefepime were unaffected. blaOXA-2 was carried on a 2910 bp partial class 1 integron containing aacA4-blaOXA-2-qacEΔ1-sul1 on an IncA/C2 plasmid, which was not present in the earlier ST258 isolates possessing blaKPC-2 with intact promoters. Hydrolysis of ertapenem by OXA-2 was confirmed using purified enzyme. Conclusions Production of OXA-2 was associated with reduced ceftazidime and ertapenem susceptibility in a K. pneumoniae ST258 isolate.

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Lee, Annabelle C., and Andrew L. Jones. "Multi-resistant Pseudomonas aeruginosa ST235 in cystic fibrosis." Paediatric Respiratory Reviews 27 (June 2018): 18–20. http://dx.doi.org/10.1016/j.prrv.2018.05.009.

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