Whole Genome Sequencing Evidences High Rates of Relapse in Clostridioides difficile Infection Caused by the Epidemic Ribotype 106

Abstract

An increasing prevalence and spread of Clostridioides difficile infection (CDI) caused by DH/NAP11/106/ST-42 has been observed worldwide, probably fostered by its great capacity to produce spores or by the higher resistance rates observed for some strains. Based on the results of our previous study where RT106 showed higher recurrence rates than other relevant ribotypes, a genetic analysis by whole-genome sequencing (WGS) of primary and recurrent RT106 isolates from ten patients was performed to determine whether the higher rate of recurrence associated with RT106 is due to relapses, caused by the same strain, or reinfections, caused by different strains. MLST profiles, resistance mutations, and phylogenetic relatedness were determined by comparative single nucleotide variant (SNV) analysis. All isolates were classified as ST42, and those belonging to the same patient were isogenic, with one exception; strains belonging to different patients were not with two exceptions, pointing to putative transmission events. Phylogenetic analysis also suggested the presence of similar local epidemic lineages associated with moxifloxacin resistance, except for one patient whose isolates clustered with different nonresistant US strains. Our results show that recurrent CDIs caused by RT06/ST42 are mainly due to relapses caused by the primary strains, showing the higher capacity of RT106/ST42 to persist and cause recurrences as compared to other ribotypes.