Antibiotic resistance and genomic features of Clostridioides difficile in southwest China

Clostridioides difficile infection (CDI) caused by toxigenic strains leads to antibiotic-related diarrhea, colitis, or even fatal pseudomembranous enteritis. Previously, we conducted a cross-sectional study on prevalence of CDI in southwest China. However, the antibiotics resistance and characteristics of genomes of these isolates are still unknown.

Antibiotic susceptibility testing with E-test strips and whole genome sequence analysis were used to characterize the features of these C. difficile isolates.

Forty-nine strains of C. difficile were used in this study. Five isolates were non-toxigenic and the rest carried toxigenic genes. We have previously reported that ST35/RT046, ST3/RT001 and ST3/RT009 were the mostly distributed genotypes of strains in the children group. In this study, all the C. difficile isolates were sensitive to metronidazole, meropenem, amoxicillin/clavulanic acid and vancomycin. Most of the strains were resistant to erythromycin, gentamicin and clindamycin. The annotated resistant genes, such as macB, vanRA, vanRG, vanRM, arlR, and efrB were mostly identified related to macrolide, glycopeptide, and fluoroquinolone resistance. Interestingly, 77.55% of the strains were considered as multi-drug resistant (MDR). Phylogenetic analysis based on core genome of bacteria revealed all the strains were divided into clade 1 and clade 4. The characteristics of genome diversity for clade 1 could be found. None of the isolates showed 18-bp deletion of tcdC as RT027 strain as described before, and polymorphism of tcdB showed a high degree of conservation than tcdA gene.

Most of the C. difficile isolates in this study were resistant to macrolide and aminoglycoside antibiotics. Moreover, the MDR strains were commonly found. All the isolates belonged to clade 1 and clade 4 according to phylogenetic analysis of bacterial genome, and highly genomic diversity of clade 1 was identified for these strains.