Pathogenicity and virulence of
            <i>Clostridioides difficile</i>

Buddle, Jessica E.; Fagan, Robert P.

doi:10.1080/21505594.2022.2150452

Cited by 46 publications

(58 citation statements)

References 256 publications

(286 reference statements)

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“…Altogether, these results show multiple characteristics related to resistance mechanisms that may contribute to the hypervirulence of the C. difficile CDC20121308 strain. The success of C. difficile as a pathogen is owed largely to its remarkable genome plasticity, allowing the acquisition of virulence factors and an array of resistance mechanisms (Buddle and Fagan, 2023). The interactions of C. difficile, an anaerobic pathogen, with the host and gut microbiota are highly intricate (Cheng and Unnikrishnan, 2023).…”

Section: Resultsmentioning

confidence: 99%

“…The phylogenetic diversity of C. difficile has allowed for the emergence of several epidemic strains in recent years (Buddle and Fagan, 2023). In particular, the ribotype (RT) 027 lineage was responsible for a 2001 North American epidemic, which spread to the UK, peaking in 2004–2006 (Rupnik et al, 2009; He et al, 2013; Buddle and Fagan, 2023). A deeper characterization of the different C. difficile RT could lead to a better understanding of C. difficile pathogenesis and host pathogen interaction.…”

Section: Resultsmentioning

confidence: 99%

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Genome sequence and characterization of a hypervirulent BI/NAP1/027Clostridioides difficile(CDC20121308)

Español,

Palumbo,

Barbero

et al. 2024

Preprint

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Clostridioides difficile is a gram-positive bacterium implicated in antibiotic-associated diarrhea. The use of antibiotics alters the gut microbiota, rendering the host susceptible to infection by C. difficile. This pathogen colonizes the large intestine of humans and animals leading to asymptomatic carriage or clinical manifestations such as toxic megacolon and fulminant colitis depending on a wide range of pathogen and host factors. The emergence of BI/NAP1/027 strains in North America and the spread of these hypervirulent ribotypes worldwide have been linked to the increase in incidence and severity of C. difficile infections (CDI) over the last decade. In this work, we aimed to characterize the BI/NAP1/027 C. difficile commercial strain CDC20121308 widely employed in the study of host-pathogen interactions. The genome sequence was obtained using a whole-genome shotgun strategy. A total of 3,717 coding sequences (CDS) and 45 tRNAs were predicted. The annotation of the CDC20121308 strain identified 26% of CDS into RAST subsystems. We also detected the presence of RT 027 lineage markers such as thyA, cdtA, cdtB and tcdC 18bp-deletion. Moreover, the genome of CDC20121308 had 11 genes devoted to resistance to toxic compounds, antibiotics (e.g. Tetracycline (Tet) and Vancomycin (Van)) and disinfecting agents as predicted using CARD. C. difficile CDC20121308 resistance to Van and Tet was confirmed by broth microdilution assay. Crystal violet staining demonstrated biofilm formation, which could be associated with antibiotic resistance and pathogenicity. Additionally, we observed a spreading diffuse growth in soft agar tubes, suggesting a motile phenotype. Lastly, a genomic region containing Type 4 Secretory System components such as virD4, virB4, and virB6 was identified. In conclusion, our results allowed a genomic and functional characterization of the BI/NAP1/027 C. difficile CDC20121308 strain. We demonstrated the presence of several genes associated with pathogenesis that were validated by experimental assays. This study provides additional data for the use of this highly virulence commercial strain of epidemiological relevance in research works involving in vitro and in vivo approaches.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Genome sequence and characterization of a hypervirulent BI/NAP1/027Clostridioides difficile(CDC20121308)

Español,

Palumbo,

Barbero

et al. 2024

Preprint

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“…This may be due to the presence of different molecules, together with the MVs present in the C. difficile culture in particular toxins that could not be fully separated from the MVs in their isolation by ultracentrifugation. C. difficile toxins are known to induce F-actin depolymerization and reorganization of the actin cytoskeleton [ 48 ], and cell death [ 49 ]. Together, toxins and MVs may be responsible for this enhanced cytotoxic effect on HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

Membrane Vesicles of Toxigenic Clostridioides difficile Affect the Metabolism of Liver HepG2 Cells

et al. 2023

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Clostridioides difficile infection (CDI) appears to be associated with different liver diseases. C. difficile secretes membrane vesicles (MVs), which may be involved in the development of nonalcoholic fatty liver disease (NALFD) and drug-induced liver injury (DILI). In this study, we investigated the presence of C. difficile-derived MVs in patients with and without CDI, and analyzed their effects on pathways related to NAFLD and DILI in HepG2 cells. Fecal extracellular vesicles from CDI patients showed an increase of Clostridioides MVs. C. difficile-derived MVs that were internalized by HepG2 cells. Toxigenic C. difficile-derived MVs decreased mitochondrial membrane potential and increased intracellular ROS compared to non-toxigenic C. difficile-derived MVs. In addition, toxigenic C. difficile-derived MVs upregulated the expression of genes related to mitochondrial fission (FIS1 and DRP1), antioxidant status (GPX1), apoptosis (CASP3), glycolysis (HK2, PDK1, LDHA and PKM2) and β-oxidation (CPT1A), as well as anti- and pro-inflammatory genes (IL-6 and IL-10). However, non-toxigenic C. difficile-derived MVs did not produce changes in the expression of these genes, except for CPT1A, which was also increased. In conclusion, the metabolic and mitochondrial changes produced by MVs obtained from toxigenic C. difficile present in CDI feces are common pathophysiological features observed in the NAFLD spectrum and DILI.

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“…Atopobium vaginae was another signi cantly abundant bacteria that may be considered diagnostic biomarkers in malnutrition and indicate poor prognosis [40]. Tannerellaceae were positively associated with the acetic acid and butyrate concentrations [41] and propionate production [42]. Clostridioides di cile was responsible for a spectrum of diseases characterized by high levels of recurrence, morbidity, and mortality [43].…”

Section: Discussionmentioning

confidence: 99%

Metagenomic analysis reveals the composition and function of intestinal microbiota were affected by different sampling methods and digestive tract segments in monogastric and polygastric animals

Guo

Shi

et al. 2023

Preprint

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Background: As a domesticated species vital to humans, cow and donkey are raised worldwide as a source of agricultural industry and food production. The digestion and absorption must rely on the division of labor and cooperation of all the digestive tract segments and microbes. The microbiota plays an important role in the health, diseases, athletic performance, weight and digestion of food in animals. The composition and function of microbial community are closely related to the animals’ physiological structure. Moreover, experimental techniques, like the sampling method, could also influence the identification results. Results: Here, using approximately 300 GB of metagenomic sequencing data from digestive tract samples from 91 samples that represent six (donkeys) and nine (cows) digestive tract segment with swab and fecal samples of monogastric (donkeys) and polygastric (cows) animals. We assembled 4,004,115 (cow) and 2,938,653 (donkey) microbial metagenome assembled contigs, and obtained 9,060,744 genes with an average of 553bp (range 102bp ~ 10,912bp) were obtained by clustering at 95% identity and 90% coverage. There were certainly influences on the microbiota with two sampling methods and fecal sample was recommended due to more abundant diversity of species compared with swab sample. Besides, microbiota in the stomach was significantly different from other segments and colon held the most abundant bacteria in the other intestine. In addition, the microbial community structure of donkey was obviously different from cow for both dominant and endemic microbes. There were 1,942 genera that were characterized by high Lactobacillus, Clostridium and Prevotella in the donkey while 1,744 genera were recognized in the cow. Differ from the donkey, different segments of the cow had different dominate genera such Prevotellafor the stomach, Kandleria for the small intestine and Clostridium for the hindgut. Conclusions: Overall, we solved the scientific problem of fecal sample could more objectively reflect the intestinal microbial community. Meanwhile, the microbial composition showed the shared and distinct features of digestive tract segments in different type animals. Our experimental design and dataset provides a valuable resource for discovery of performance-enhancing microbes and systematic studies of cow and donkey microbiome.

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Pathogenicity and virulence of Clostridioides difficile

Cited by 46 publications

References 256 publications

Genome sequence and characterization of a hypervirulent BI/NAP1/027Clostridioides difficile(CDC20121308)

Genome sequence and characterization of a hypervirulent BI/NAP1/027Clostridioides difficile(CDC20121308)

Membrane Vesicles of Toxigenic Clostridioides difficile Affect the Metabolism of Liver HepG2 Cells

Metagenomic analysis reveals the composition and function of intestinal microbiota were affected by different sampling methods and digestive tract segments in monogastric and polygastric animals

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