Microbial interactions of Clostridioides difficile

C. difficile is a spore-forming anaerobic bacterium that can cause gut infections in both humans and animals. Pathogenicity of C. difficile is influenced by the bacterium responding to different competing pressures such as colonisation fitness and resistance to phages, and the acquisition of genetic elements conferring such fitness/resistance. In the gut, C. difficile is involved in three major forms of interactions: chemical interactions with itself (e.g. quorum sensing), alteration in gene expression in response to the presence of other bacteria, and horizontal gene transfer. For instance, C. difficile interacts with Enterococci and phages via horizontal gene transfer, and changes its gene expression in the presence of certain fungal species. Such microbial interactions contribute to the evolution of C. difficile, seen through intra-species genome comparisons and analyses, and could affect the outcome of C. difficile colonisation and pathogenicity. This is most clearly seen with certain probiotics which prevent C. difficile infection (CDI), and faecal microbiota transplantation (FMT) for treatment of recurrent CDI. Interactions with other microbes have also changed the epidemiology of CDI over the past 20 years while zoonoses have played an ever more important role. However, there is much more to be learned about the cellular, transcriptomic, genomic, proteomic, and epidemiological/transmission effects of interacting phages, bacteria, bacterial extracellular vesicles, animal viruses, fungi, and parasites. At the same time, the role of the environmental conditions, such as biofilms and other matrices, where such events occur, is underappreciated. There is also much more to learn about C. difficile as an influencer of other pathogens.

Although it is almost impossible to consider microbial interactions without other components such as host cells, diet, and nutrients, the scope is more strictly defined here for convenience and feasibility. To recognise the importance of other microbes involved in modifying C. difficile, this research topic is focused on assembling current knowledge on microbial interactions with C. difficile, moving towards studies not limited to mixed-microbe analyses, modelling, and genome analyses to gain insight into the bacterium’s myriad of “social” networks that contribute to disease, treatment, transmission, or simply bacterial survival.