Invasive fungal infections affect over two million people per year world-wide and kill more people each year than either malaria, TB, breast cancer or prostate cancer. Bloodstream infections caused by Candida species (candidaemia) are the most frequent life-threatening invasive fungal infections, with the majority caused by Candida albicans. Invasive C. albicans infections result in sepsis, and even when treated with antifungal drugs, over 40% of invasive Candida infections are fatal.
Over 60% of humans have C. albicans in their gastrointestinal (GI) tract and this represents a major risk factor for developing fatal invasive candidiasis. In healthy individuals, this pathogen is kept in check by competition with the gut bacterial microbiota, intact intestinal epithelial barriers, and by the host’s immune system. However, if the status of these host defences changes, e.g. during cancer chemotherapy, immunotherapy, or organ or stem cell transplantation, then C. albicans can escape the gut, disseminate through the blood and cause systemic disease.
In a pilot study which utilised a novel in vitro model that we developed to simulate the human colon microenvironment, we identified bacterial species in faecal samples from healthy adult donors that kill C. albicans. We are currently expanding our list of anti-Candida bacterial species and will test whether the application of these potential therapeutic bacterial species can clear C. albicans from our in vitro colon model, as well as an ex vivo gut organoid model.
The overall aim is to demonstrate the feasibility of a non-invasive, targeted microbial therapeutic which clears C. albicans from the GI tract to prevent life-threatening disease. Our novel strategy represents a new way of thinking with respect to the management of invasive candidiasis, providing an alternative to current clinical reliance on antifungal drugs which do not always prevent death, and against which resistance is emerging.