Project Details
Projekt
Genetic circuits underlying fungal-bacterial interactions in the mammalian intestine
Applicant
Christian Perez, Ph.D.
Subject Area
Parasitology and Biology of Tropical Infectious Disease Pathogens
Term
from 2016 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 316048879
Our microbiota is composed of representatives of all three domains of life, i.e. bacteria, archaea and eukaryotes. Little is known, however, about how non-bacterial members of the microbiota interact with the host and with other cohabiting microbes. Here, I describe experiments to investigate the interplay between Candida albicans, the most prevalent fungus in the human gut, and other members of the microbiota as well as the host. Preliminary work conducted in my laboratory indicates that several genetic determinants of in vivo fitness in this fungus are influenced by the gut microbiota. Based on these observations, I specifically propose to: (1) Determine whether C. albicans relies on a microbiota-derived molecule as a key source of nitrogen to proliferate in the mammalian gut. The in vivo and in vitro characterization of C. albicans strains harboring deletions in putative allantoate transporters will allow me to accomplish this goal. (2) Establish how the microbiota shapes the interface between C. albicans and the mammalian intestinal lining. Immunohistochemistry of intestinal sections of germ-free and conventionally raised mice inoculated with C. albicans wild-type or adherence-impaired mutants will be used to achieve this aim. (3) Establish whether in vivo fitness determinants in the human gut bacterial commensal Bacteroides thetaiotaomicron are influenced by C. albicans. I will evaluate the patterns of colonization in gnotobiotic mice mono- or co-associated with these species to attain this goal. The proposed research is expected to reveal basic principles underlying in vivo interactions among C. albicans, the gut microbiota and the host. Furthermore, since C. albicans overgrowth in the gut is a major source of life-threatening infections, our findings will allow us to devise potential interventions that target the gut flora to prevent these infections.
DFG Programme
Priority Programmes
