Molecular epidemiology of Clostridioides (Clostridium) difficile
Clostridioides (formerly Clostridium) difficile is a strictly anaerobic Gram-positive spore-forming bacillus. It is currently the most frequent cause of healthcare-associated infectious diarrhea in industrialized countries. Patients suffering from C. difficile infection (CDI) experience various clinical symptoms ranging from mild watery diarrhea and abdominal pain, to fulminant diarrhea, pseudomembranous colitis and death. Major outbreaks have been reported in Europe and North America, especially here in Quebec in 2003-2004. The economic impact of CDI on the healthcare system is huge: in USA, ~500,000 cases are reported each year, for a total annual cost estimated to $3.2 billions. This pathogen is now spreading worldwide and cases have been reported in South America, several European countries, in Asia and Australia.
Fundamental and epidemiological research on C. difficile has intensified over the last 15 years. CDI pathogenesis is a multifactorial and complex process that not only involves the pathogen itself, but that also implies the host immune system and metabolism as well as commensal bacteria from the gut. We also have to consider the way antibiotics are prescribed in medicine, since CDI occurs as a consequence of antibiotic treatments. At the moment, there are more questions than answers, and with the aging population that is particularly at risk and continuously increasing, the problem of CDI will most likely persist in the future. Therefore, it will be crucial in the next years to better understand fundamental biological processes in C. difficile (e.g. virulence, evolution and host-pathogen interactions), and to better know the factors that predispose to CDI so that we can change the way we approach CDI prevention and treatment. There is also an urgent need for new therapeutic strategies because current treatment options against this multidrug-resistant pathogen are very limited, and recurrent infections are a problem. Fecal microbiota transplantation is currently one of the most effective means to treat recurrent CDI, but this “crude” therapeutic strategy needs further refinement.
Our research aims at better understanding the epidemiology of CDI, the contribution of antibiotics in the process of infection, how bacteriophages, and especially prophages, can impact on C. difficile virulence and lifestyle. We possess a collection of nearly 1,000 clinical isolates with corresponding clinical data. Full genome sequences have been obtained for several isolates. Whole genome comparisons are underway to understand genetic diversity, and mobile genetic elements, in particular prophages, are among key players.
New molecular tools (e.g. CRISPR-Cas, allelic exchange, etc.) are now available to genetically manipulate the genome of C. difficile. We have such tools in our lab, and we also have access to a mouse model of CDI to test different strains and mutants in an in vivo context.