Comparative genomic and transmission analysis of <i>Clostridioides difficile</i> between environmental, animal, and clinical sources in China

Zhou, Yanzi; Zhou, Wangxiao; Xiao, Tingting; Chen, Yunbo; Lv, Tao; Wang, Yuan; Zhang, Shuntian; Cai, Hongliu; Chi, Xiaohui; Kong, Xiaoyang; Zhou, Kai; Shen, Ping; Shan, Tongling; Xiao, Yonghong

doi:10.1080/22221751.2021.2005453

Cited by 15 publications

(15 citation statements)

References 52 publications

(67 reference statements)

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“…It is interesting to note that we found clade 4 and clade 5 strains with unusual STs (37, 35, 41, 48, 55, 95, and ST708) among Mexican isolates. Some of these STs have been isolated from different environmental, animal, and clinical sources (26) but are now circulating among humans and emerging as clinically important strains.…”

Section: Discussionmentioning

confidence: 99%

Genomic and phenotypic studies amongClostridioides difficileisolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea

Meléndez Sánchez,

Hernández,

Ares

et al. 2024

Preprint

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Clostridioides difficileis the most common cause of healthcare-associated infection worldwide. Its pathogenesis is mainly due to the production of toxins A, B, and CDT, whose genetic variants may be associated with disease severity. We studied genetic diversity inC. difficileisolates from hospitalized adults and children using different gene and genome typing methods and investigated their association with in vitro expression of toxins.Whole-genome was sequenced in 39 toxigenicC. difficileisolates and used for multilocus sequence typing (MLST),tcdA, andtcdBtyping sequence type, and for phylogenetic analysis. Strains were grown in broth media, and expression of toxin genes was measured by real-time PCR and cytotoxicity was determined in culture assays.We found that clustering after genome-wide phylogeny followed clade classification, although different clusters were identified within each clade. The toxin profiletcdA+/tcdB+/cdtA+/cdtB+ and clade 2/ST1 were the most prevalent among isolates from children and adults. Isolates presented two TcdA and three TcdB subtypes, of which A2 and B2 were dominant. Toxin gene expression or cytotoxicity were not associated with genotyping or toxin subtypes. In conclusion, genomic and phenotypic analysis shows high diversity amongC. difficileisolates from patients with healthcare-associated-diarrhea.ImportanceClostridioides difficileis a toxin-producing bacterial pathogen associated with healthcare, and different genetic or phenotypic typing have been proposed for classification. We extensively studied cytotoxicity, expression of toxins, whole genome phylogeny, and toxin typing in clinicalC. difficileisolates. Most isolates presented atcdA+ tcdB+cdtA+ cdtB+pattern, with high diversity in cytotoxicity, and clade 2/ST1 was the most prevalent. However, they all had the same TcdA2/TcdB2 toxin subtype. Advances in genomics and bioinformatics tools offer the opportunity to understand the virulence ofC. difficilebetter and find markers with better clinical use.

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Section: Discussionmentioning

confidence: 99%

Genomic and phenotypic studies amongClostridioides difficileisolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea

Meléndez Sánchez,

Hernández,

Ares

et al. 2024

Preprint

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“…In two instances (ST3-NT and ST15) we observed environmental and dog isolates differing by two or fewer SNPs. A study in China identified close genetic overlap with C. difficile isolates across all three reservoirs [42], although they used a core genome analysis with a distant outgroup and the effective core genome space was likely too small to clearly identify transmissions (see below). Although one study sampled the environment, pigs, and farmers within a single farm and failed to identify any zoonotic transmission [97], another study found genotypic overlap between isolates from humans and non-human animals [43].…”

Section: Discussionmentioning

confidence: 99%

“…This apparently near ubiquitous presence is likely due to the pathogen's ability to form oxygen resistant spores [34] and persist in a dormant state until a new mammalian host is found [37]. The potential transmission of C. difficile between animals and humans has been investigated [38][39][40][41][42], though direct transmission of C. difficile between animals and humans has only been rarely reported [43,44]. Although researchers have described C. difficile as omnipresent in humans, non-human animals, and the environment, a causal connection between environmental C. difficile isolates and human or animal disease is difficult to definitively demonstrate [17,41].…”

Section: Introductionmentioning

confidence: 99%

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A local-scale One Health genomic surveillance of Clostridioides difficile demonstrates highly related strains from humans, canines, and the environment

et al. 2023

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Although infections caused by Clostridioides difficile have historically been attributed to hospital acquisition, growing evidence supports the role of community acquisition in C. difficile infection (CDI). Symptoms of CDI can range from mild, self-resolving diarrhoea to toxic megacolon, pseudomembranous colitis, and death. In this study, we sampled C. difficile from clinical, environmental, and canine reservoirs in Flagstaff, Arizona, USA, to understand the distribution and transmission of the pathogen in a One Health framework; Flagstaff is a medium-sized, geographically isolated city with a single hospital system, making it an ideal site to characterize genomic overlap between sequenced C. difficile isolates across reservoirs. An analysis of 562 genomes from Flagstaff isolates identified 65 sequence types (STs), with eight STs being found across all three reservoirs and another nine found across two reservoirs. A screen of toxin genes in the pathogenicity locus identified nine STs where all isolates lost the toxin genes needed for CDI manifestation (tcdB, tcdA), demonstrating the widespread distribution of non-toxigenic C. difficile (NTCD) isolates in all three reservoirs; 15 NTCD genomes were sequenced from symptomatic, clinical samples, including two from mixed infections that contained both tcdB+ and tcdB- isolates. A comparative single nucleotide polymorphism (SNP) analysis of clinically derived isolates identified 78 genomes falling within clusters separated by ≤2 SNPs, indicating that ~19 % of clinical isolates are associated with potential healthcare-associated transmission clusters; only symptomatic cases were sampled in this study, and we did not sample asymptomatic transmission. Using this same SNP threshold, we identified genomic overlap between canine and soil isolates, as well as putative transmission between environmental and human reservoirs. The core genome of isolates sequenced in this study plus a representative set of public C. difficile genomes (n=136), was 2690 coding region sequences, which constitutes ~70 % of an individual C. difficile genome; this number is significantly higher than has been published in some other studies, suggesting that genome data quality is important in understanding the minimal number of genes needed by C. difficile . This study demonstrates the close genomic overlap among isolates sampled across reservoirs, which was facilitated by maximizing the genomic search space used for comprehensive identification of potential transmission events. Understanding the distribution of toxigenic and non-toxigenic C. difficile across reservoirs has implications for surveillance sampling strategies, characterizing routes of infections, and implementing mitigation measures to limit human infection.

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“…In China, one of the dominant circulating RTs is RT017 [ 59 , 137 , 138 ]. However, another study published in 2021 on samples from different sources (e.g., soil, animals) found that the predominant RTs in China are RT001, RT046, and RT596 [ 139 ]. In 2021, the study by Zhao et al found that the most common clade in the Asian country is clade 4 [ 101 ].…”

Section: Worldwide Distribution Of C Difficile Rib...mentioning

confidence: 99%

Make It Less difficile: Understanding Genetic Evolution and Global Spread of Clostridioides difficile

Mengoli

Barone

Fabbrini

et al. 2022

Genes

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Clostridioides difficile is an obligate anaerobic pathogen among the most common causes of healthcare-associated infections. It poses a global threat due to the clinical outcomes of infection and resistance to antibiotics recommended by international guidelines for its eradication. In particular, C. difficile infection can lead to fulminant colitis associated with shock, hypotension, megacolon, and, in severe cases, death. It is therefore of the utmost urgency to fully characterize this pathogen and better understand its spread, in order to reduce infection rates and improve therapy success. This review aims to provide a state-of-the-art overview of the genetic variation of C. difficile, with particular regard to pathogenic genes and the correlation with clinical issues of its infection. We also summarize the current typing techniques and, based on them, the global distribution of the most common ribotypes. Finally, we discuss genomic surveillance actions and new genetic engineering strategies as future perspectives to make it less difficile.

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Comparative genomic and transmission analysis of Clostridioides difficile between environmental, animal, and clinical sources in China

Cited by 15 publications

References 52 publications

Genomic and phenotypic studies amongClostridioides difficileisolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea

Genomic and phenotypic studies amongClostridioides difficileisolates show a high prevalence of clade 2 and great diversity in clinical isolates from Mexican adults and children with healthcare-associated diarrhea

A local-scale One Health genomic surveillance of Clostridioides difficile demonstrates highly related strains from humans, canines, and the environment

Make It Less difficile: Understanding Genetic Evolution and Global Spread of Clostridioides difficile

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