Evolutionary dynamics of Clostridium difficile over short and long time scales

Abstract

Clostridium difficile has rapidly emerged as the leading cause of antibiotic-associated diarrheal disease, with the transcontinental spread of various PCR ribotypes, including 001, 017, 027 and 078. However, the genetic basis for the emergence of C. difficile as a human pathogen is unclear. Whole genome sequencing was used to analyze genetic variation and virulence of a diverse collection of thirty C. difficile isolates, to determine both macro and microevolution of the species. Horizontal gene transfer and large-scale recombination of core genes has shaped the C. difficile genome over both short and long time scales. Phylogenetic analysis demonstrates C. difficile is a genetically diverse species, which has evolved within the last 1.1–85 million years. By contrast, the disease-causing isolates have arisen from multiple lineages, suggesting that virulence evolved independently in the highly epidemic lineages.

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

“…630 (RT 012), mobile elements accounted for ~10% of the genome and included a plasmid, prophages, transposons, IStrons, genomic islands, CRISPRs and a skin element (Sebaihia et al, 2006). This has remained consistent in the annotated genomes of other strains published since, including M120 (clade 5), and R20291 (clade 2) (He et al, 2010;Stabler et al, 2009). …”

“…Similar rates have been calculated for RT 078 and RT 027 (He et al, 2013;Knetsch et al, 2014). These rates are much higher than the estimated long-term evolutionary rate (He et al, 2010). This difference may be due to the effects of purifying selection purging deleterious mutations over time.…”

“…A recent examination of PubMLST data (http://pubmlst.org/cdifficile/) shows at least two other cryptic clades which we will term C-II and C-III (Figure 2). Clade 5, the most divergent of the non-cryptic clades is estimated to have diverged from the rest of the species between 1.1 and 85 million years ago (He et al, 2010). Given the lack of research in many geographical regions, there are…”

The host immune response to Clostridium difficile infection

“…Although a degree of cross reactivity has been observed for particular vaccine candidates , future therapies may have to take into account the continual evolution of the C. difficile species and emergence of new genetically distinct clades [Cairns et al 2012;Stabler et al 2006Stabler et al , 2012He et al 2010]. Monitoring both the genetic diversity and epidemiology of circulating C. difficile strains may enable a prediction of newly emerging genetically distinct strain types that are able to cause severe disease or epidemics.…”

MLST revisited: the gene-by-gene approach to bacterial genomics

“…A popular method has been to construct phylogenies on the basis of SNPs (single-nucleotide differences among samples) that have been identified either by the mapping of short-read sequence data to a reference genome, or by aligning de novo-assembled sequences to a reference genome 37,40 . This approach has been used successfully to investigate the epidemiology and evolution of a number of single-clone pathogens or members of the same lineage [41][42][43][44][45][46][47][48][49][50][51][52] , but it is limited by its requirement for a reference sequence or whole-genome alignment 40 . The analysis of diverse or highly recombining organisms in this way will prove challenging because the number of total polymorphisms increases as the number of polymorphisms conforming to a clonal model of descent decreases (BOX 1).…”