Thibaut Vanbaelen , Christophe Van Dijck , Jolein Laumen , Natalia Gonzalez , Irith De Baetselier , Sheeba S. Manoharan-Basil , Tessa De Block , Chris Kenyon
{"title":"Global epidemiology of antimicrobial resistance in commensal Neisseria species: A systematic review","authors":"Thibaut Vanbaelen , Christophe Van Dijck , Jolein Laumen , Natalia Gonzalez , Irith De Baetselier , Sheeba S. Manoharan-Basil , Tessa De Block , 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}
Ziyu Yang , Bijun Qiu , Danhong Cheng , Na Zhao , Yao Liu , Min Li , Qian Liu
{"title":"Virulent Staphylococcus aureus colonizes pediatric nares by resisting killing of human antimicrobial peptides","authors":"Ziyu Yang , Bijun Qiu , Danhong Cheng , Na Zhao , Yao Liu , Min Li , 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}
V. de Lastours , I. El Meouche , F. Chau , J. Beghain , D. Chevret , A. Aubert-Frambourg , O. Clermont , G. Royer , O. Bouvet , E. Denamur , B. Fantin , for the CIPHARES Group
{"title":"Evolution of fluoroquinolone-resistant Escherichia coli in the gut after ciprofloxacin treatment","authors":"V. de Lastours , I. El Meouche , F. Chau , J. Beghain , D. Chevret , A. Aubert-Frambourg , O. Clermont , G. Royer , O. Bouvet , E. Denamur , B. Fantin , 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}
Greg Turner , Michael O’Grady , Daniel Hudson , Xochitl Morgan , Frank Frizelle , Rachel Purcell
{"title":"Rectal swabs are a reliable method of assessing the colonic microbiome","authors":"Greg Turner , Michael O’Grady , Daniel Hudson , Xochitl Morgan , Frank Frizelle , 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 < 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}
Terence Lee , Stanley Pang , Denise A. Daley , Julie C. Pearson , Sam Abraham , Geoffrey W. Coombs
{"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 , Stanley Pang , Denise A. Daley , Julie C. Pearson , Sam Abraham , 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}
Iqra Bashir Nehvi , Neha Quadir , Mohd Khubaib , Javaid Ahmad Sheikh , Mohd Shariq , Krishnaveni Mohareer , Sharmistha Banerjee , Syed Asad Rahman , Nasreen Z. Ehtesham , Seyed E. Hasnain
{"title":"ArgD of Mycobacterium tuberculosis is a functional N-acetylornithine aminotransferase with moonlighting function as an effective immune modulator","authors":"Iqra Bashir Nehvi , Neha Quadir , Mohd Khubaib , Javaid Ahmad Sheikh , Mohd Shariq , Krishnaveni Mohareer , Sharmistha Banerjee , Syed Asad Rahman , Nasreen Z. Ehtesham , 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}
Huiluo Cao , Kelvin Hei-Yeung Chiu , Susan S. Chiu , Shuo Jiang , Kin-Hung Chow , Pak-Leung Ho
{"title":"Genomic investigation of a Streptococcus pneumoniae serotype 24F strain causing meningoencephalitis in Hong Kong","authors":"Huiluo Cao , Kelvin Hei-Yeung Chiu , Susan S. Chiu , Shuo Jiang , Kin-Hung Chow , 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}
Magdalena Nüesch-Inderbinen , Marc J.A. Stevens , Nicole Cernela , Andrea Müller , Michael Biggel , Roger Stephan
{"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 , Marc J.A. Stevens , Nicole Cernela , Andrea Müller , Michael Biggel , 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}
{"title":"MicroRNA hsa-let-7a facilitates staphylococcal small colony variants survival in the THP-1 macrophages by reshaping inflammatory responses","authors":"Agnieszka Magryś, Agnieszka Bogut","doi":"10.1016/j.ijmm.2021.151542","DOIUrl":"10.1016/j.ijmm.2021.151542","url":null,"abstract":"<div><p>Recent studies have provided emerging evidence of the critical involvement of microRNAs in host immune defence against bacterial infection and that likewise the expression of the miRNAs is profoundly impacted by a variety of pathogens to subvert the immune response. Here, we report the role of hsa-let-7a miRNA in response to <em>Staphylococcus epidermidis</em> Small Colony Variants infection. We also assessed whether the expression levels of inflammatory cytokines associated with the hsa-let-7a are manipulated by the pathogen and the effect of the IFN-γ priming on the expression of hsa-let-7a and the fate of SCVs/WTs in infected macrophages. A striking observation was the downregulation of the let-7a miRNA upon challenge of the THP-1 activated cells with the SCV isolates while no significant changes in expression were noticed after the infection of macrophages with their WT counterparts. <em>Staphylococcus epidermidis</em> WT and SCV strains were found to invade and survive in macrophages. A significant reduction in bacterial load for both phenotypes was observed in macrophages treated with let-7a mimic compared to untreated ones. Survival of WTs was augmented in cells treated with the inhibitor in 4 out of 5 strains as compared to the number of bacteria recovered from non-transfected cells. At the same time, let-7a inhibitor did not influence on the survival of SCVs in macrophages as their number was comparable to number recovered from non-transfected cells. When the ratio of both let-7a cytokine targets was compared, anti-inflammatory IL-10 cytokine was induced by SCVs predominantly, while the macrophage challenge with WTs was characterized by the inflammatory cytokine profile with high IL-6 and low IL-10 production. Moreover, the balance between pro-inflammatory and anti-inflammatory cytokines has been expectedly retrieved when macrophages were transfected with let-7a mimic before infection with WT or SCV strains. The results also show that IFN-γ likely regulates the macrophage environment contributing to the inflammatory response and elimination of bacteria from intracellular milieu by augmenting the synthesis of pro-inflammatory cytokines and supressing the anti-inflammatory IL-10. Our work has shown that SCVs have the potential to regulate the let-7a miRNA to balance the pro-inflammatory IL-6 with anti-inflammatory IL-10 and this mechanism is one of the ways in a complex regulatory network adopted by SCVs to promote their survival.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"311 8","pages":"Article 151542"},"PeriodicalIF":4.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000710/pdfft?md5=eb9e3b1210b111d3520fe4943d114b26&pid=1-s2.0-S1438422121000710-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39691258","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}
Alina Dietrich, Ursula Steffens, Peter Sass , Gabriele Bierbaum
{"title":"The hypersusceptible antibiotic screening strain Staphylococcus aureus SG511-Berlin harbors multiple mutations in regulatory genes","authors":"Alina Dietrich, Ursula Steffens, Peter Sass , Gabriele Bierbaum","doi":"10.1016/j.ijmm.2021.151545","DOIUrl":"10.1016/j.ijmm.2021.151545","url":null,"abstract":"<div><p>The genetic plasticity of <em>Staphylococcus aureus</em> has facilitated the evolution of many virulent and drug-resistant strains. Here we present the sequence of the 2.74 Mbp genome of <em>S. aureus</em> SG511-Berlin, which is frequently used for antibiotic screening. Although <em>S. aureus</em> SG511 and the related methicillin-resistant <em>S. aureus</em> MRSA252 share a high similarity in their core genomes, indicated by an average nucleotide identity (ANI) of 99.83%, the accessory genomes of these strains differed, as nearly no mobile elements and resistance determinants were identified in the genome of <em>S. aureus</em> SG511. Susceptibility testing showed that <em>S. aureus</em> SG511 was susceptible to most of the tested antibiotics of different classes. Intriguingly, and in contrast to the standard laboratory strain <em>S. aureus</em> HG001, <em>S. aureus</em> SG511 was even hyper-susceptible towards cell wall and membrane targeting agents, with the exception of the MurA-inhibitor fosfomycin. In depth comparative genome analysis revealed that, in addition to the loss of function mutation in the antibiotic sensor histidine kinase gene <em>graS</em>, further mutations had occurred in the lysyltransferase gene <em>mprF</em>, the structural giant protein gene <em>ebh</em>, and the regulator genes <em>codY</em> and <em>saeR</em>, which might contribute to antibiotic susceptibility. In addition, an insertion element in <em>agrC</em> abolishes Agr-activity in <em>S. aureus</em> SG511, and the <em>spa</em> and <em>sarS</em> genes, which encode the surface protein SpA and its transcriptional regulator, were deleted. Thus, the lack of mobile resistance genes together with multiple mutations affecting cell envelope morphology may render <em>S. aureus</em> SG511 hyper-susceptible towards most cell wall targeting agents.</p></div>","PeriodicalId":50312,"journal":{"name":"International Journal of Medical Microbiology","volume":"311 8","pages":"Article 151545"},"PeriodicalIF":4.1,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1438422121000746/pdfft?md5=5e7920143648397133bbddc02713b747&pid=1-s2.0-S1438422121000746-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829550","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}