Global evolutionary dynamics and resistome analysis of Clostridioides difficile ribotype 017.
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ABSTRACT:
SUBMITTER: Imwattana K
PROVIDER: S-EPMC9176289 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
Global evolutionary dynamics and resistome analysis of <i>Clostridioides difficile</i> ribotype 017.
Imwattana Korakrit K Putsathit Papanin P Collins Deirdre A DA Leepattarakit Teera T Kiratisin Pattarachai P Riley Thomas V TV Knight Daniel R DR
Microbial genomics 20220301 3
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Project description:We describe imipenem-resistant and imipenem-susceptible clinical isolates of Clostridium difficile ribotype 017 in Portugal. All ribotype 017 isolates carried an extra penicillin-binding protein gene, pbp5, and the imipenem-resistant isolates had additional substitutions near the transpeptidase active sites of pbp1 and pbp3. These clones could disseminate and contribute to imipenem resistance.
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Project description:Clostridioides difficile sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for C. difficile ST37 isolates. The 325 ST37 genomes from six continents, including North America (n = 66), South America (n = 4), Oceania (n = 7), Africa (n = 9), Europe (n = 138) and Asia (n = 101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibiotic-resistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, tcdB mRNA levels, and sporulation capacities (P < 0.001). Kyoto Encyclopedia of Genes and Genomes analysis showed 10 metabolic pathways were significantly enriched in the mutations among isolates associated with severe CDI (P < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of tcdR and negatively to the expression of toxin repressor genes, ccpA and codY. In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of C. difficile ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in C. difficile ST37 isolates.
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Project description:Clostridium difficile is an important nosocomial pathogen and the leading cause of antibiotic-associated diarrhea. Multilocus sequence typing indicates that C. difficile strains belong to five distinct genetic clades encompassing several PCR ribotypes (RT). Since their emergence in 2003, hypervirulent RT027 strains have been a major focus of research; in contrast, our current understanding of RT017-mediated disease pathogenesis lags far behind. In this study, we aimed to characterize host immunity to CF5 and M68, two genetically well-defined RT017 strains. Both strains engaged with host Toll-like receptor 2/6 (TLR2/6), TLR2-CD14, and TLR5 to similar extents in a model cell line. Despite this, CF5 mediated significantly greater dendritic cell (DC) interleukin-12 (IL-12), IL-27, and IL-10 immunity than M68. Both strains elicited similar IL-1β mRNA levels, and yet only M68 caused a marked increase in secretory IL-1β. A CF5 cocultured-DC cytokine milieu drove an equipotent Th1 and Th17 response, while M68 promoted greater Th17 immunity. Human gastrointestinal ex vivo cytokine responses to both strains were characterized. Taken together, our data suggest that C. difficile strains mediate overlapping and yet distinct mucosal and DC/T cell immunity. Finally, toxin-driven IL-1β release supports the hypothesis that this cytokine axis is a likely target for therapeutic intervention for C. difficile infection.
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Project description:The objective of this study was to analyse the genetic relatedness of Clostridioides difficile polymerase chain reaction ribotype 017 (RT017) strains from patients with hospital-acquired C. difficile infection (HA-CDI) in a hospital with a high RT017 prevalence. From 2009 to 2013, 200 RT017 strains (26.8%) were collected from 745 HA-CDI patient isolates. They comprised 64 MLVA types, and 197 (98.5%) strains were genetically related to 5 clonal complexes (CCs). The largest cluster, CC-A, included 163 isolates of 40 MLVA types. CC-A accounted for 20% of RT017 strains in 2009 and sharply increased to 94.9% in 2010, 94% in 2011, 86.2% in 2012, and 73.5% in 2013. The other 4 CCs included 20 isolates with 7 MLVA types. The resistance rates of antimicrobials were as follows: clindamycin 100%, moxifloxacin 99%, rifaximin 88.5%, and vancomycin 1%. All isolates were susceptible to metronidazole and piperacillin/tazobactam. Comparing antibiotic resistance among CCs, the geometric mean of the minimum inhibitory concentrations of moxifloxacin, vancomycin, and piperacillin/tazobactam were significantly higher for CC-A isolates than for the other CCs. RT017 clones constantly evolved over the 5 years studied with regard to genetic relatedness. The levels of antibiotic resistance may contribute to the persistence of organisms in the institution.
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Project description:The Evolutionary Adventures of Clostridioides difficile ribotype 017
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Project description:The diarrheal pathogen Clostridium difficile consists of at least six distinct evolutionary lineages. The RT017 lineage is anomalous, as strains only express toxin B, compared to strains from other lineages that produce toxins A and B and, occasionally, binary toxin. Historically, RT017 initially was reported in Asia but now has been reported worldwide. We used whole-genome sequencing and phylogenetic analysis to investigate the patterns of global spread and population structure of 277 RT017 isolates from animal and human origins from six continents, isolated between 1990 and 2013. We reveal two distinct evenly split sublineages (SL1 and SL2) of C. difficile RT017 that contain multiple independent clonal expansions. All 24 animal isolates were contained within SL1 along with human isolates, suggesting potential transmission between animals and humans. Genetic analyses revealed an overrepresentation of antibiotic resistance genes. Phylogeographic analyses show a North American origin for RT017, as has been found for the recently emerged epidemic RT027 lineage. Despite having only one toxin, RT017 strains have evolved in parallel from at least two independent sources and can readily transmit between continents.
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Project description:Clostridium difficile PCR ribotype 017 global strains
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Project description:Genomic analysis of a diverse collection of Clostridioides difficile ribotype 078 isolates from Ireland and 9 countries in Europe provided evidence for complex regional and international patterns of dissemination that are not restricted to humans. These isolates are associated with C. difficile colonization and clinical illness in humans and pigs.
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Project description:Clostridium difficile ribotype 017 project
| PRJEB2105 | ENA
Project description:Clostridium difficile ribotype (RT) 017 is an important toxigenic C. difficile RT which, due to a deletion in the repetitive region of the tcdA gene, only produces functional toxin B. Strains belonging to this RT were initially dismissed as nonpathogenic and circulated largely undetected for almost two decades until they rose to prominence following a series of outbreaks in the early 2000s. Despite lacking a functional toxin A, C. difficile RT 017 strains have been shown subsequently to be capable of causing disease as severe as that caused by strains producing both toxins A and B. While C. difficile RT 017 strains can be found in almost every continent today, epidemiological studies suggest that the RT is endemic in Asia and that the global spread of this MLST clade 4 lineage member is a relatively recent event. C. difficile RT 017 transmission appears to be mostly from human to human with only a handful of reports of isolations from animals. An important feature of C. difficile RT 017 strains is their resistance to several antimicrobials and this has been documented as a possible factor driving multiple outbreaks in different parts of the world. This review summarizes what is currently known regarding the emergence and evolution of strains belonging to C. difficile RT 017 as well as features that have allowed it to become an RT of global importance.
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