Clostridioides difficile as a Potential Pathogen of Importance to One Health: A Review

Abstract
Clostridioides difficile (basonym Clostridium) is a bacterial enteropathogen associated with cases of C. difficile infection that can result in pseudomembranous colitis, rapid fluid loss, and death. For decades following its isolation, C. difficile was thought to be a solely nosocomial pathogen, being isolated from individuals undergoing antimicrobial therapy and largely affecting elderly populations. More recently, C. difficile spores have been identified in the broader environment, including in food-producing animals, soil, and food matrices, in both ready-to-eat foods and meat products. Furthermore, evidence has emerged of hypervirulent ribotypes (RTs), such as RT078, similar to those cultured in asymptomatic carriers, also being identified in these environments. This finding may reflect on adaptations arising in these bacteria following selection pressures encountered in these niches, and which occurs due to an increase in antimicrobial usage in both clinical and veterinary settings. As C. difficile continues to adapt to new ecological niches, the taxonomy of this genus has also been evolving. To help understand the transmission and virulence potential of these bacteria of importance to veterinary public health, strategies applying multi-omics-based technologies may prove useful. These approaches may extend our current understanding of this recognized nosocomial pathogen, perhaps redefining it as a zoonotic bacterium. In this review, a brief background on the epidemiological presentation of C. difficile will be highlighted, followed by a review of C. difficile in food-producing animals and food products. The current state of C. difficile taxonomy will provide evidence of Clade 5 (ST11/RT078) delineation, as well as background on the genomic elements linked to C. difficile virulence and ongoing speciation. Recent studies applying second- and third-generation sequencing technologies will be highlighted, and which will further strengthen the argument made by many throughout the world regarding this pathogen and its consideration within a One Health dimension.