C. difficile RT078 Frequently Transfers Between Livestock, Humans, Irrespective of Geographic Origins

Trevor Lawley, PhD, Host-Microbiota Interactions Laboratory at Wellcome Trust Sanger Institute in Hinxton

Trevor Lawley, PhD

The Clostridium difficile RT078 strain is an emerging global threat to human and animal health, and this evolutionary distinct C. difficile lineage frequently spreads between humans and animals with no apparent geographic barrier, according to study findings from researchers at the Wellcome Sanger Institute.¹

“Not all bacteria differentiate between human and farm animals; a warm intestinal tract is really what they’re looking for,” said Trevor Lawley, PhD, Host-Microbiota Interactions Laboratory at Wellcome Trust Sanger Institute in Hinxton, United Kingdom, told MD Magazine. “We have to consider the bigger picture. Overall, what this paper shows is that there are some lineages that exist in the healthcare system that can also be found in animals.”

Investigators collected worldwide diverse C. difficile RT078 samples and extracted DNA with phenol-chloroform. In total, 247 C. difficile strains were collected between 1996 to 2012 from North America, Europe, Australia and Asia. Strains were derived from humans (n= 183) and animals (cattle, horses, pigs, poultry [n= 59]).

Of the 182 C. difficile RT078 strains obtained, genomes were sequenced and combined with 65 previously collected RT078 samples. The investigators evaluated the phylogenetic structure of the RT078 strain by using core genome maximum likelihood phylogeny of the obtained C. difficile RT078 strains and comparing these against the reference genome from C. difficile M120 strains (n= 248). Additionally, investigators explored the phylogenetic strain distribution between humans and animals to determine the possibility of zoonotic transfer.

According to the analysis, the investigators discovered a bidirectional spread of the C. difficile RT078 strain between humans and animals as well as evidence of human-to-human and animal-to-animal spread.

An additional analysis of related RT078 strains found a total of 6 clusters containing human and animal isolates with similar whole genomes (ANI, ≥99.73%). Interestingly, Cluster 1 in this analysis contained human strains from the UK and animal strains from Canada, suggesting that zoonotic spread was not limited to a specific geographic region. Based on these findings, the investigators suggest the RT078 strain is now a global threat.

Also, the investigators found a total of 22 different putative antimicrobial resistance genes in the genomes of the C. difficile RT078 strains, the most frequent of which included chromosome-encoded cdeA.

While uncertainty exists as to the original reservoir of C. difficile RT078, the findings of reciprocal transmission of the strain between humans and livestock “emphasizes the importance of a comprehensive ‘One Health’ perspective in managing and controlling C. difficile RT078.”

Simply, the “One Health” idea involves the connection between human and animal health and how this relates to their shared environment.

“There are some variants of C. difficile that move between farm animals and humans,” Lawley said. “We often think of a pathogen as being linked to only one type of host, but one of the biggest conclusions of this study is that that idea is not so simple — we really want to look at the epidemiology of C. difficile than the actual source. Ultimately, this is more about the diagnostics side, but this study confirms an idea that already existed.”

REFERENCE

1. Knetsch CW, Kumar N, Forster SC, et al. Zoonotic Transfer of Clostridium difficile Harboring Antimicrobial Resistance between Farm Animals and Humans. J Clin Microbiol. 2018;56(3).