A global to local genomics analysis ofClostridioides difficileST1/RT027 identifies cryptic transmission events in a northern Arizona healthcare network

Abstract

AbstractClostridioides difficileis a ubiquitous, diarrheagenic pathogen often associated with healthcare-acquired infections that can cause a range of symptoms from mild, self-limiting disease to toxic megacolon and death. Since the early 2000s, a large proportion ofC. difficilecases have been attributed to the ribotype 027 (RT027) lineage, which is associated with sequence type 1 (ST1) in theC. difficilemultilocus sequence typing (MLST) scheme. The spread of ST1 has been attributed, in part, to resistance to fluoroquinolones used to treat un-related infections, which creates conditions ideal forC. difficilecolonization and proliferation. In this study, we analyzed 27 isolates from a healthcare network in northern Arizona, USA, and 1,352 public ST1 genomes to place locally-sampled isolates into a global context. Core genome, single nucleotide polymorphism (SNP) analysis demonstrated that at least 6 separate introductions of ST1 were observed in healthcare facilities in northern Arizona over an 18-month sampling period. A reconstruction of transmission networks identified potential nosocomial transmission of isolates following two of these introductions, which were only identified via whole genome sequence analysis. Antibiotic resistance heterogeneity was observed among ST1 genomes, including variability in resistance profiles among locally sampled ST1 isolates. To investigate why ST1 genomes are so common globally, we compared all high-qualityC. difficilegenomes and identified that ST1 genomes have gained and lost a number of genomic regions compared to all otherC. difficilegenomes; analyses of other toxigenicC. difficilesequence types demonstrates that this loss may be anomalous and could be related to niche specialization. These results suggest that a combination of antimicrobial resistance and gain and loss of specific genes may explain the prominent association of this sequence type withC. difficileinfection cases worldwide. The degree of genetic variability in ST1 suggests that classifying all ST1 genomes into a quinolone-resistant hypervirulent clone category may not be appropriate. Whole genome sequencing of clinicalC. difficileisolates provides a high-resolution surveillance strategy for monitoring persistence and transmission ofC. difficileand for assessing the performance of infection prevention and control strategies.