International Journal of Medical Microbiology最新文献

{"title":"Treponema pallidum Tp0751 alters the expression of tight junction proteins by promoting bEnd3 cell apoptosis and IL-6 secretion","authors":"Simin Lu ,&nbsp;Jianye Wang ,&nbsp;Zhangping He ,&nbsp;Siqin He ,&nbsp;Kang Zheng ,&nbsp;Man Xu ,&nbsp;Shuai Yuan ,&nbsp;Yimou Wu","doi":"10.1016/j.ijmm.2022.151553","DOIUrl":"10.1016/j.ijmm.2022.151553","url":null,"abstract":"<div><h3>Background</h3><p>Neurosyphilis is a serious complication caused by the invasion of the central nervous system by <em>Treponema pallidum subsp. pallidum</em> (<em>T. pallidum</em>). However, the molecular mechanism by which <em>T. pallidum</em> crosses the blood-brain barrier has not been fully elucidated.</p></div><div><h3>Objectives</h3><p>The primary purpose of this experimental design was to explore the effect of the <em>T. pallidum</em> adhesion protein Tp0751 on the blood-brain barrier and cerebrovascular endothelial cells.</p></div><div><h3>Methods</h3><p>BEnd3 cells were used to construct a monolayer blood-brain barrier model in vitro. The integrity of blood-brain barrier model was evaluated by a transendothelial cell resistance meter and transmission electron microscope after the stimulation of recombinant protein TP0751. Hoechst 33258 staining and flow cytometry were used to detect the apoptosis rate. Western blotting assay was used to measure the expression of tight junction proteins and apoptosis-related proteins. The enzyme activity detection kit was responsible for detecting the enzyme activities of Caspase 3, Caspase 8 and Caspase 9. The expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 at the transcription and translation levels were detected by qRT-PCR and ELISA, respectively.</p></div><div><h3>Results</h3><p>The results showed that, the tight junction structures between cells showed no obvious fragmentation, but the levels of the tight junction proteins zonula occludens-1 and occludin were reduced by the effects of Tp0751 on bEnd3 cells. In addition, further research demonstrated that after incubation with bEnd3 cells, Tp0751 induced cell apoptosis in a concentration- and time-dependent manner via the caspase 8/caspase 3 pathway. These apoptotic processes may have contributed to the changes in tight junction proteins expression. Furthermore, the Tp0751 protein may be involved in the pathogenic process by which <em>T. pallidum</em> crosses the blood-brain barrier by promoting secretion of the proinflammatory factor interleukin-6.</p></div><div><h3>Conclusions</h3><p>On the whole, this study is the first to reveal and highlight that Tp0751 may affect the expression of tight junction proteins by inducing apoptosis and promoting the secretion of the inflammatory cytokine IL-6, thus playing a role in the progression of neurosyphilis caused by <em>T. pallidum</em>.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 4","pages":"Article 151553"},"PeriodicalIF":4.1,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000066/pdfft?md5=23b7e00b78977ae4c73e783709fe8c3f&pid=1-s2.0-S1438422122000066-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128209089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the cagA-gene in Helicobacter pylori in Mongolia and detection of two EPIYA-A enriched CagA types","authors":"Oyunbaatar Altanbayar ,&nbsp;Avarzed Amgalanbaatar ,&nbsp;Chimeddorj Battogtokh ,&nbsp;Narmandakh Bayarjargal ,&nbsp;Dana Belick ,&nbsp;Malte Kohns Vasconcelos ,&nbsp;Colin R. Mackenzie ,&nbsp;Klaus Pfeffer ,&nbsp;Birgit Henrich","doi":"10.1016/j.ijmm.2022.151552","DOIUrl":"10.1016/j.ijmm.2022.151552","url":null,"abstract":"<div><p><em>Helicobacter pylori</em> infection is strongly associated with gastritis, gastroduodenal ulcer disease and gastric carcinoma. The virulence of <em>H. pylori</em> strains increases with the presence of the pathogenicity island PAI, which encodes a Type 4 Secretion System and the oncoprotein CagA. Two major CagA types can be distinguished by differences in the repetitive EPIYA region in the C-terminal sequence; the more virulent East Asian CagA type with EPIYA-A, -B, and -D motifs and the Western CagA type with EPIYA-A, -B, and C motifs, the virulence of which is associated with the multitude of EPIYA-C motifs.</p><p>In this study, the <em>cag</em>A gene was characterized in <em>H. pylori</em> strains isolated from Mongolians suffering from gastritis (80%) or ulcer (20%). The EPIYA region of 53 isolates was determined by PCR-amplification of overlapping <em>cag</em>A regions and subsequent Sanger sequencing. Only one <em>H. pylori</em> isolate carried the East Asian type (ABD) and 52 isolates the Western type of CagA, thereof 30 the EPIYA type ABC, 19 the ABCC type and one each of type ABCCCC, AAABC and AAAAB. An amino acid exchange from EPIY<strong>A</strong>-B to EPIY<strong>T</strong>-B was predominantly found in CagA proteins in strains with &lt; 2 EPIYA-C copies (n = 25/32; p = 0.015) including the two EPIYA-A enriched CagA proteins, which have not been described to date. Due to the amino acid triplet preceding the EPIYA motif and strength of predicted phosphorylation, the multiple EPIYA-A motifs A2, A3 and A4 were shown to cluster with EPIYA-B and EPIYT-B with the unique feature of amino acid E in position − 4 to Y of EPIYA. It has been described that tyrosine-phosphorylated EPIYA-A and -B motifs counteract the EPIYA-C-driven signaling towards host cell transformation and malignancy. Thus, Mongolian <em>H. pylori</em> strains carrying CagA proteins not only with a few EPIYA-C segments but also with multiplied EPIYA-A segments are probably less virulent; a thesis that needs further investigation at the protein level.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 3","pages":"Article 151552"},"PeriodicalIF":4.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000054/pdfft?md5=9a4c488ef670b2f2b9c34cf8ccaf5699&pid=1-s2.0-S1438422122000054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121372323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global epidemiology of antimicrobial resistance in commensal Neisseria species: A systematic review","authors":"Thibaut Vanbaelen ,&nbsp;Christophe Van Dijck ,&nbsp;Jolein Laumen ,&nbsp;Natalia Gonzalez ,&nbsp;Irith De Baetselier ,&nbsp;Sheeba S. Manoharan-Basil ,&nbsp;Tessa De Block ,&nbsp;Chris Kenyon","doi":"10.1016/j.ijmm.2022.151551","DOIUrl":"10.1016/j.ijmm.2022.151551","url":null,"abstract":"<div><h3>Background</h3><p>Commensal <em>Neisseria</em> species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic <em>Neisseria</em> spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal <em>Neisseria</em> spp<em>.</em> and how this has evolved over time. We also aimed to assess if commensal <em>Neisseria</em> spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin.</p></div><div><h3>Methods</h3><p>Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal <em>Neisseria</em> spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal <em>Neisseria</em> spp.</p></div><div><h3>Results</h3><p>A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal <em>Neisseria</em> spp. We did find evidence of an increasing trend in MICs of commensal <em>Neisseria</em> spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal <em>Neisseria</em> spp.</p></div><div><h3>Conclusion</h3><p>The MICs of commensal <em>Neisseria</em> spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 3","pages":"Article 151551"},"PeriodicalIF":4.1,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000042/pdfft?md5=b8ea8456cca2b1b855d2e92764c21919&pid=1-s2.0-S1438422122000042-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133083847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virulent Staphylococcus aureus colonizes pediatric nares by resisting killing of human antimicrobial peptides","authors":"Ziyu Yang ,&nbsp;Bijun Qiu ,&nbsp;Danhong Cheng ,&nbsp;Na Zhao ,&nbsp;Yao Liu ,&nbsp;Min Li ,&nbsp;Qian Liu","doi":"10.1016/j.ijmm.2022.151550","DOIUrl":"10.1016/j.ijmm.2022.151550","url":null,"abstract":"<div><h3>Background</h3><p>The nasal carriage of <em>Staphylococcus aureus</em> introduces risks for subsequent infections, the rate of which is particularly high in children. The colonization mechanisms of <em>S. aureus</em> are not fully understood.</p></div><div><h3>Methods</h3><p>The epidemiological characteristics of nasal colonizing strains from pediatric patients undergoing liver transplantation and healthy pre-school children were analyzed first. Phenotypes, including biofilm formation and hemolytic activity, were tested for all the isolates. Bacterial pathogenicity indicated by a mouse skin abscess model and resistance to antimicrobial peptides (AMPs) was compared between the predominant genotypes from each group.</p></div><div><h3>Results</h3><p>The ST188 clone dominated in healthy children, whereas ST59 was prevalent for the pediatric patients. Although ST22 was the second most abundant genotype in the patient group, it was rarely found in healthy children. Interestingly, the colonizing ST59 and ST22 genotypes were more virulent, as indicated by the increased ability for hemolysis in vitro and severe subcutaneous abscesses in the mouse model, compared with ST188. We observed that the virulent ST59 and ST22 displayed higher resistance to antibiotics compared with ST188. Most of the ST59 and ST22 were methicillin-resistant <em>S. aureus</em> (MRSA), and all of the ST188 strains were methicillin-susceptible (MSSA). Moreover, we observed that the virulent ST59 and ST22 can resist killing by human antimicrobial peptides (AMPs). Mechanically, upon stimulation by AMPs, the virulent <em>S. aureus</em> can induce high expression of a phenol-soluble modulin transporter (Pmt) system.</p></div><div><h3>Conclusion</h3><p>Pediatric patients can be colonized by virulent <em>S. aureus</em> clones, which are able to resist AMPs’ killing through the Pmt system. The residence of virulent strains necessitates the continuous monitoring of potential infections, as well as annealing, to take protective decolonization measures.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 2","pages":"Article 151550"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000030/pdfft?md5=61961791de3709d8724567d0b4e82700&pid=1-s2.0-S1438422122000030-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39958318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution of fluoroquinolone-resistant Escherichia coli in the gut after ciprofloxacin treatment","authors":"V. de Lastours ,&nbsp;I. El Meouche ,&nbsp;F. Chau ,&nbsp;J. Beghain ,&nbsp;D. Chevret ,&nbsp;A. Aubert-Frambourg ,&nbsp;O. Clermont ,&nbsp;G. Royer ,&nbsp;O. Bouvet ,&nbsp;E. Denamur ,&nbsp;B. Fantin ,&nbsp;for the CIPHARES Group","doi":"10.1016/j.ijmm.2022.151548","DOIUrl":"10.1016/j.ijmm.2022.151548","url":null,"abstract":"<div><h3>Background</h3><p>Three healthy volunteers carried similar quinolone-resistant <em>E. coli</em> (QREC) (pulsed field gel electrophoresis profiles) in their gut before and after 14 days ciprofloxacin treatment. Given the intensity of the selective pressure and the mutagenic properties of quinolones, we determined whether these strains had evolved at the phenotypic and/or genomic levels.</p></div><div><h3>Material and methods</h3><p>Commensal QREC from before day-0 (D0), and a month after 14 days of ciprofloxacin (D42) were compared in 3 volunteers. Growth experiments were performed; acetate levels, mutation frequencies, quinolone MICs and antibiotic tolerance were measured at D0 and D42. Genomes were sequenced and single nucleotide polymorphisms (SNPs) between D0 and D42 were analyzed using DiscoSNP and breseq methods. Cytoplasmic proteins were extracted, HPLC performed and proteins identified using X!tandem software; abundances were measured by mass spectrometry using the Spectral Counting (SC) and eXtraction Ion Chromatograms (XIC) integration methods.</p></div><div><h3>Results</h3><p>No difference was found in MICs, growth characteristics, acetate concentrations, mutation frequencies, tolerance profiles, phylogroups, O-and H-types, <em>fimH</em> alleles and sequence types between D0 and D42. No SNP variation was evidenced between D0 and D42 isolates for 2/3 subjects; 2 SNP variations were evidenced in one. At the protein level, very few significant protein abundance differences were identified between D0 and D42.</p></div><div><h3>Conclusion</h3><p>No fitness, tolerance, metabolic or genomic evolution of commensal QREC was observed overtime, despite massive exposure to ciprofloxacin in the gut. The three strains behaved as if they had been unaffected by ciprofloxacin, suggesting that gut may act as a sanctuary where bacteria would be protected from the effect of antibiotics and survive without any detrimental effect of stress.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 2","pages":"Article 151548"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000017/pdfft?md5=6bf8f4e11c38fa8928a043356d5b0f02&pid=1-s2.0-S1438422122000017-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39820923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rectal swabs are a reliable method of assessing the colonic microbiome","authors":"Greg Turner ,&nbsp;Michael O’Grady ,&nbsp;Daniel Hudson ,&nbsp;Xochitl Morgan ,&nbsp;Frank Frizelle ,&nbsp;Rachel Purcell","doi":"10.1016/j.ijmm.2022.151549","DOIUrl":"10.1016/j.ijmm.2022.151549","url":null,"abstract":"<div><h3>Background</h3><p>Advances in genome sequencing have enabled detailed microbiome analysis; however, the ideal specimen type for sequencing is yet to be determined. Rectal swabs may offer a rapid and convenient modality for colonic microbiome analysis. The aim of this study is to evaluate the use of rectal swabs compared to faecal specimens.</p></div><div><h3>Methods and results</h3><p>Twenty health professionals participated in this study and provided a faecal specimen, a self-collected rectal swab and a rectal swab taken by a clinician. DNA was extracted and 16S rRNA gene sequencing was carried out for microbiome analysis.</p><p>Alpha diversity was higher in swabs compared to faecal specimens; however, the difference was only significant when comparing clinician-obtained swabs to faeces.</p><p>Analysis of beta diversity consistently showed that few taxa were affected by sample type. We found sample type accounted for only 6.8% of community variation (R2 = 0.067, p &lt; 0.001, permanova). Notably, there were only six genera identified in clinician-obtained swabs that were not also found in the self-taken swabs.</p></div><div><h3>Conclusions</h3><p>Both self-collected and clinician obtained rectal swabs are a reliable method of analysing the colonic microbiome. Obtaining specimens for microbiome analysis is often time-critical due to therapy, such as antibiotics, influencing the microbiome. Rectal swabs are shown to be a valid and convenient modality for microbiome analysis.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 2","pages":"Article 151549"},"PeriodicalIF":4.1,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422122000029/pdfft?md5=471aa0c44e6c251e0abaac9717582175&pid=1-s2.0-S1438422122000029-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39884836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The changing molecular epidemiology of Enterococcus faecium harbouring the van operon at a teaching hospital in Western Australia: A fifteen-year retrospective study","authors":"Terence Lee ,&nbsp;Stanley Pang ,&nbsp;Denise A. Daley ,&nbsp;Julie C. Pearson ,&nbsp;Sam Abraham ,&nbsp;Geoffrey W. Coombs","doi":"10.1016/j.ijmm.2021.151546","DOIUrl":"10.1016/j.ijmm.2021.151546","url":null,"abstract":"<div><h3>Introduction</h3><p><em>Enterococcus faecium</em> is an opportunistic pathogen that has become one of the leading causes of hospital acquired infection that are resistant to multiple critically important antimicrobials.</p></div><div><h3>Aim</h3><p>The objective of the study was to describe the molecular characteristics and relationship between major strains of <em>E. faecium</em> harbouring the van operon and to determine if the strains had increasing virulence and antimicrobial resistance determinants over time.</p></div><div><h3>Methods</h3><p><em>E. faecium</em> harbouring the van operon detected using PCR from surveillance rectal swabs of patients that were admitted to high-risk units at a Perth teaching hospital from 2001 to 2015 were retrospectively analysed using a whole genome sequencing and bioinformatics approach.</p></div><div><h3>Results</h3><p>ST18, ST78, ST80, ST173, ST203 and ST555 were identified as the major STs accounting for 93.7% of <em>E. faecium</em> isolates. Except for ST173, major STs identified at Royal Perth Hospital (RPH) have been reported across Australia and internationally. Isolates from each ST formed independently branched phylogenetic clusters with each harbouring unique virulence and antimicrobial resistance profiles. Depending on the ST, different genes conferring resistance to similar antimicrobial classes were identified. Except for ST80 which harboured the vanA type operon, all major strains harboured the vanB operon conferring only vancomycin resistance.</p></div><div><h3>Conclusion</h3><p>Major strains of <em>E. faecium</em> isolated over 15-years showed unique virulome and resistome profiles with no indication of increasing virulence or antimicrobial resistance determinants. Strains were distantly related and the acquisition of different genes encoding similar antimicrobial resistances suggest the independent evolution of each strain.</p></div><div><h3>Data Summary</h3><p>The whole genome sequences of all isolates from this study are accessible from the NCBI-SRA database under project number PRJNA575940 and PRJNA524213. Published reference sequence Aus0004 was obtained from NCBI-SRA under project number PRJNA86649 DOI:10.1128/JB.00259–12</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 1","pages":"Article 151546"},"PeriodicalIF":4.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000758/pdfft?md5=d6611e087ca743832dcc1732ffc0ec59&pid=1-s2.0-S1438422121000758-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39613451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator","authors":"Iqra Bashir Nehvi ,&nbsp;Neha Quadir ,&nbsp;Mohd Khubaib ,&nbsp;Javaid Ahmad Sheikh ,&nbsp;Mohd Shariq ,&nbsp;Krishnaveni Mohareer ,&nbsp;Sharmistha Banerjee ,&nbsp;Syed Asad Rahman ,&nbsp;Nasreen Z. Ehtesham ,&nbsp;Seyed E. Hasnain","doi":"10.1016/j.ijmm.2021.151544","DOIUrl":"10.1016/j.ijmm.2021.151544","url":null,"abstract":"<div><p><em>Mycobacterium tuberculosis (M. tuberculosis)</em> encodes an essential enzyme acetyl ornithine aminotransferase ArgD (Rv1655) of arginine biosynthetic pathway which plays crucial role in <em>M. tuberculosis</em> growth and survival<em>.</em> ArgD catalyzes the reversible conversion of N-acetylornithine and 2 oxoglutarate into glutamate-5-semialdehyde and L-glutamate. It also possesses succinyl diaminopimelate aminotransferase activity and can thus carry out the corresponding step in lysine biosynthesis. These essential roles played by ArgD in amino acid biosynthetic pathways highlight it as an important metabolic chokepoint thus an important drug target. We showed that <em>M. tuberculosis</em> ArgD rescues the growth of Δa<em>rgD E. coli</em> grown in minimal media validating its functional importance. Phylogenetic analysis of <em>M. tuberculosis</em> ArgD showed homology with proteins in gram positive bacteria, pathogenic and non-pathogenic mycobacteria suggesting the essentiality of this protein. ArgD is a secretory protein that could be utilized by <em>M. tuberculosis</em> to modulate host innate immunity as its moonlighting function. <em>In-silico</em> analysis predicted it to be a highly antigenic protein. The recombinant ArgD protein when exposed to macrophage cells induced enhanced production of pro-inflammatory cytokines TNF, IL6 and IL12 in a dose dependent manner. ArgD also induced the increased production of innate immune effector molecule NOS2 and NO in macrophages. We also demonstrated ArgD mediated activation of the canonical NFkB pathway. Notably, we also show that ArgD is a specific TLR4 agonist involved in the activation of pro-inflammatory signaling for sustained production of effector cytokines. Intriguingly, ArgD protein treatment activated macrophages to acquire the M1 phenotype through the increased surface expression of MHCII and costimulatory molecules CD80 and CD86. ArgD induced robust B-cell response in immunized mice, validating its antigenicity potential as predicted by the <em>in-silico</em> analysis. These properties of <em>M. tuberculosis</em> ArgD signify its functional plasticity that could be exploited as a possible drug target to combat tuberculosis.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"312 1","pages":"Article 151544"},"PeriodicalIF":4.1,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000734/pdfft?md5=f3892d1c537062c179c95772d8e589d9&pid=1-s2.0-S1438422121000734-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39613452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic investigation of a Streptococcus pneumoniae serotype 24F strain causing meningoencephalitis in Hong Kong","authors":"Huiluo Cao ,&nbsp;Kelvin Hei-Yeung Chiu ,&nbsp;Susan S. Chiu ,&nbsp;Shuo Jiang ,&nbsp;Kin-Hung Chow ,&nbsp;Pak-Leung Ho","doi":"10.1016/j.ijmm.2021.151543","DOIUrl":"10.1016/j.ijmm.2021.151543","url":null,"abstract":"<div><p>Pneumococcal conjugate vaccines (PCVs) successfully decreased the incidence of invasive pneumococcal disease in children. However, many countries have reported serotype replacement and a rebound in diseases from non-vaccine serotypes. Here, we report the genomic investigation of a <em>Streptococcus pneumoniae</em> strain M215 that caused severe meningoencephalitis in an infant in 2019. The strain was assigned to serotype 24F using the bioinformatic pipeline SeroBA and pneumococcal type specific anti-sera. The strain was resistant to cotrimoxazole from mutations in both folA and folP genes. It was susceptible to penicillin and other non-β-lactam antibiotics. Phylogenetically, it belongs to Global Pneumococcal Sequence Cluster (GPSC) 6 and multi-locus sequence type 162. A total of 38 virulence genes were detected in the genome of M215. Upon comparison of the profile of virulence genes, GPSC6 but not non-GPSC6 strains of serotype 24F and related serotypes were found to possess the major virulence determinant, pilus islet-1, comprising genes encoding sortases (<em>srtB, srtC, srtD</em>), pilus proteins (<em>rrgA, rrgB</em> and <em>rrgC</em>) and one transcriptional regulator (<em>rlrA</em>), which was previously described to be characteristic feature of international clones in the pre-PCV era. In our locality, this represented the first detection of serotype 24F and GPSC6/ST162 causing serious pneumococcal disease. The emergence of the non-vaccine serotype 24F GPSC6/ST162 lineage with molecular feature of high virulence is concerning and emphasizes the need for full characterization of strains causing severe disease.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"311 8","pages":"Article 151543"},"PeriodicalIF":4.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000722/pdfft?md5=16ccaa1f163759fd5dc890d0eb5da2ef&pid=1-s2.0-S1438422121000722-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39691257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution of virulence factors, antimicrobial resistance genes and phylogenetic relatedness among Shiga toxin-producing Escherichia coli serogroup O91 from human infections","authors":"Magdalena Nüesch-Inderbinen ,&nbsp;Marc J.A. Stevens ,&nbsp;Nicole Cernela ,&nbsp;Andrea Müller ,&nbsp;Michael Biggel ,&nbsp;Roger Stephan","doi":"10.1016/j.ijmm.2021.151541","DOIUrl":"10.1016/j.ijmm.2021.151541","url":null,"abstract":"<div><p>Shiga toxin-producing <em>Escherichia coli</em> (STEC) belonging to the serogroup O91 are among the most common non-O157 STEC serogroups associated with human illness in Europe. This study aimed to analyse the virulence factors, antimicrobial resistance genes and phylogenetic relatedness among 48 clinical STEC O91 isolates collected during 2003–2019 in Switzerland. The isolates were subjected to whole genome sequencing using short-read sequencing technologies and a subset of isolates additionally to long-read sequencing. They belonged to O91:H10 (n<!--> <!-->=<!--> <!-->6), O91:H14 (n<!--> <!-->=<!--> <!-->40), and O91:H21 (n<!--> <!-->=<!--> <!-->2). Multilocus sequence typing showed that the O91:H10 isolates all belonged to sequence type (ST)641, while the O91:H14 isolates were assigned to ST33, ST9700, or were non-typeable. Both O91:H21 isolates belonged to ST442. Shiga toxin gene <em>stx1a</em> was the most common Shiga toxin gene subtype among the isolates, followed by <em>stx2b</em>, <em>stx2d</em> and <em>stx2a</em>. All isolates were LEE-negative and carried one or two copies of the IrgA adhesin gene <em>iha</em>. In a subset of long-read sequenced isolates, modules of the Locus of Adhesion and Autoaggregation pathogenicity island (LAA-PAI) carrying <em>iha</em> and other genes such as <em>hes</em>, <em>lesP</em> or <em>agn43</em> were identified. A large proportion of STEC O91:H14 carried the subtilase cytotoxin gene <em>subA</em>, colicin genes (<em>cba</em>, <em>cea</em>, <em>cib</em> and <em>cma</em>) or microcin genes (<em>mcmA</em>, <em>mchB</em>, <em>mchC</em> and <em>mchF</em>). STEC O91:H14 were further distinguished from STEC O91:H10/H21 by one or more virulence factors found in extraintestinal pathogenic <em>E. coli</em> (ExPEC), including <em>hlyF</em>, <em>iucC/iutA</em>, <em>kpsE</em> and <em>traT</em>. The <em>hlyF</em> gene was identified on a novel mosaic plasmid that was unrelated to <em>hlyF</em>+ plasmids described previously in STEC. Core genome phylogenetic analysis revealed that STEC O91:H10 and STEC O91:H21 were clonally conserved, whereas STEC O91:H14 were clonally diverse. Among three STEC O91:H14 isolates, a number of resistance genes were identified, including genes that mediate resistance to aminoglycosides (<em>aadA</em>, <em>aadA2</em>, <em>aadA9</em>, <em>aadA23</em>, <em>aph(3'')-Ib</em> and <em>aph(6)-Id</em>), chloramphenicol (<em>cmlA</em>), sulphonamides (<em>sul2</em> and <em>sul3</em>), and trimethoprim (<em>drfA12</em>). Our data contribute to understanding the genetic diversity and differing levels of virulence potential within the STEC O91 serogroup.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"311 8","pages":"Article 151541"},"PeriodicalIF":4.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000709/pdfft?md5=d604d4c8bc20494f2f46e229cc299611&pid=1-s2.0-S1438422121000709-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39607589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}