Mechanisms of host colonization by a eukaryotic member of the microbiota

• Applicant: Christian Perez, Ph.D.
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 285290031

Human mucosal surfaces are laden with trillions of microorganisms from all three domains of life--microbes that play key roles in human health and disease. The long-term goal of my research program is to understand the tactics employed by these microorganisms to thrive in the host and elucidate what goes awry when some of them transition from harmless commensals to life-threatening pathogens. To address these questions, I study the most prominent fungal species living in humans, Candida albicans, which is a normal commensal in our gut but can also colonize other tissues and spread into the bloodstream causing deep-seated, often fatal infections. Using genetic screens in mouse models of infection, I recently identified two C. albicans transcription regulators, RTG1 and RTG3, that direct the colonization of the mammalian host. Building upon this work, this proposal describes a combination of in vitro, in vivo and animal experiments aimed at elucidating the mechanisms whereby these regulators mediate host colonization. Specifically, I propose to (1) establish how Rtg1/3 promote the colonization of the mammalian gastrointestinal tract; (2) uncover the mechanism(s) whereby Rtg1/3 are activated and identify the signaling molecule(s) that feed into these regulators; and (3) determine how the ectopic expression of RTG1/3 promotes the dissemination of C. albicans from the gut into the bloodstream. Achieving these goals will not only lead to a fuller understanding of the nature of the interactions with our own microbiota--C. albicans in particular--but also open potential avenues of intervention for populations at risk of developing fatal infections caused by microbes that spread from our mucosal surfaces into the bloodstream.

• DFG Programme: Research Grants