New fungal infection understanding could produce better treatments
Fungi are usually harmless to humans, and can be found on the skin and in the body. Some species however can pose a significant health threat. “Human fungal pathogens are responsible for a vast array of infections, and some of these can be deadly,” says FunHoMic project coordinator Christophe d’Enfert from the Institut Pasteur in France. “In fact, three main types – Candida, Aspergillus and Cryptococcus – are responsible for about 1.5 million deaths worldwide every year. While antifungal treatments exist, these are not always very efficient, and there has been an increase in antifungal resistance.”
Host genetics, fungal genetics and microbiota diversity
The FunHoMic project, which was supported by the Marie Skłodowska-Curie Actions programme, sought to better understand the interplay between fungal infections and the host. “There are in fact three interacting components here – the fungus; the host; and the microbiota,” explains d’Enfert. Your microbiota is the collection of bacteria, viruses, fungi and other microorganisms in and around your body. “Our aim was to look at host genetics, fungal genetics and microbiota diversity, to see how variations in these components might influence infections.” The project team focused on one particular species – Candida albicans – which is responsible for the largest number of fungal infections in immune-compromised patients in hospitals.
New technologies to study fungi
The project brought together 13 PhD students and introduced new technologies to the study of fungal infections. These technologies included organ-on-a-chip. Here, 3D microfluidic cell cultures are integrated into a circuit chip, which then simulates the activities and mechanics of an organ system. “We also used fermenters that can mimic the gastrointestinal tract, and applied new tools to analyse fungal microbiota,” says d’Enfert. “Fungi make up a much smaller fraction of the microbiota than bacteria and have been less studied.” Other students examined how genetic diversity in C. albicans can influence infection. A subgroup of C. albicans isolates for example was found to only cause infections in the vagina. “We were able to demonstrate the inability of this group of Candida to thrive in other niches such as the gastrointestinal tract and the bloodstream,” adds d’Enfert. “We were then able to pinpoint this inability to a number of genetic markers.” The project also studied a fungal vaginal infection that affects about 80 % of women throughout their lifetime, and is often recurrent. Genetic factors that could be responsible were examined, along with different immune responses. Students also attempted to identify bacteria that are antagonistic to Candida, and could hold potential as probiotic treatments.
On the road to new discoveries and treatments
For d’Enfert, the project has been hugely successful in training students in this particular field, as well as identifying potential technologies and techniques that could lead to new treatments. New avenues of research include why some people harbour C. albicans while others do not, as well as the impact of factors such as diet on infection rates. “This project hasn’t ended these infections, but it has helped us to make significant progress along the road to a better understanding,” he remarks. “In terms of potential applications, we’ve been able to identify potential new probiotics, and generated a great deal of knowledge about Candida infections and the susceptibility of some hosts to fungal infections.”
Keywords
FunHoMic, fungal, infection, microbiota, genetics, Candida, fungi, immune
