How adaptation of Candida albicans to inflammatory mediators impacts immune recognition and pathogenesis.

• Applicant: Dr. Mark Gresnigt
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 434385622

The yeast Candida albicans has been a harmless commensal on mucosal surfaces and particularly the gastrointestinal tract for long periods in human evolution. However, today’s healthcare, including the use of broad-spectrum antibiotics that eradicate protective microbiota, and cytostatic therapies that interfere with the intestinal barrier and immune system, predisposes to opportunistic C. albicans infections.Immune mediators have been demonstrated to be sensed by bacterial pathogens and induce adaptations that promote virulence. For several reasons, adaptation to the host inflammatory environment may also play a significant role in the pathogenesis of C. albicans infections. First, the co-existence of C. albicans with the human host likely supported co-evolution of adaptation strategies that support either a commensal or a pathogenic lifestyle. Second, scarce published proof along with my unpublished preliminary data suggests that C. albicans can sense immune mediators such as cytokines and consequently cause a change in behaviour. Yet, systematic studies investigating C. albicans’ adaptation to immune mediators are lacking. Moreover, it remains unknown whether such adaptations, induced by immune mediators, may increase the virulence of the fungus, or play a key role in repressing virulence characteristics, thereby supporting commensalism. Furthermore, it is unknown how such fungal adaptations, in turn, influence the induction of host defence mechanisms as well as the pathogenesis of infections. Therefore, in my proposed project the objectives are to understand and investigate (i) how C. albicans senses and adapts to the inflammatory environment, (ii) how the immune system in turn senses, responds to and counteracts these adaptations, and (iii) how this impacts pathogenesis.This project combines the expertise areas of immunology, mycology, and host-pathogen interactions, in which I have been developing my skills since the beginning of my scientific career. As host for my project, I selected the Hans-Knöll-Institute in Jena, which facilitates close collaborations with world-leading experts on infection biology of C. albicans and excellent scientific facilities. The studies are designed to expand our understanding on how the inflammatory environment regulates fungal responses and adaptation to the host and could provide leads for design of therapies aimed at blocking the pathogenicity mechanisms to improve the outcome of Candida infections.

• DFG Programme: Independent Junior Research Groups