Genomic evolution and virulence association of <i>Clostridioides difficile</i> sequence type 37 (ribotype 017) in China

Abstract

<i>Clostridioides difficile</i> 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 <i>C. difficile</i> ST37 isolates. The 325 ST37 genomes from six continents, including North America (<i>n</i> = 66), South America (<i>n</i> = 4), Oceania (<i>n</i> = 7), Africa (<i>n</i> = 9), Europe (<i>n</i> = 138) and Asia (<i>n</i> = 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, <i>tcdB</i> mRNA levels, and sporulation capacities (<i>P</i> < 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 (<i>P</i> < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of <i>tcdR</i> and negatively to the expression of toxin repressor genes, <i>ccpA</i> and <i>cod</i>Y. In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of <i>C. difficile</i> ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in <i>C. difficile</i> ST37 isolates.