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

• Final Report Year: 2021

Final Report Abstract

The fungus Candida albicans is a ubiquitous member of the human gut microbiota, yet also causes mucosal disease and life-threatening disseminated infections. The research project that I conducted sought to explore the links between the fungus’ facet as intestinal commensal and its ability to proliferate in disparate organs. Through systematic genetic screens conducted in mouse models of gut colonization and oropharyngeal candidiasis, we have found that fungal genetic determinants of fitness in the gut also shape the interactions of the fungus with other tissues. The study provided advances in several directions: (i) established that a regulator of fungal sphingolipids governs colonization of the gastrointestinal tract and facilitates disseminated infections; (ii) revealed a regulatory gene that explicitly governs persistence of the fungus in the oral cavity and fitness during vaginal infections; and (iii) demonstrated that the location, distribution and morphology of the fungus are strongly influenced by the presence/absence of gut microbiota. Taken together, the project uncovered novel principles underlying the interplay between mammalian host and the most prominent fungus residing in humans.

Publications

• (2017) The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice. PLoS Pathog 13: e1006699
  Böhm L, Torsin S, Tint SH, Eckstein MT, Ludwig T, Pérez JC
  
• (2018) Diversification of DNA binding specificities enabled SREBP transcription regulators to expand the repertoire of cellular functions that they govern in fungi. PLoS Genetics 14: e1007884
  del Olmo Toledo V, Puccinelli R, Fordyce PM, Pérez JC
  
• (2018) Identification of Candida albicans regulatory genes governing mucosal infection. Cell Microbiol 20: e12841
  Meir J, Hartman E, Eckstein MT, Guiducci E, Kirchner F, Rosenwald A, LeibundGut- Landmann S, Pérez JC
  
• (2019) Remasking of Candida albicans β-Glucan in response to environmental pH is regulated by quorum sensing. mBio 10: e02347-19
  Cottier F, Sherrington S, Cockerill S, del Olmo Toledo V, Kissane S, Tournu H, Orsini L, Palmer GE, Pérez JC, Hall RA
  
• (2020) The regulatory proteins Rtg1/3 govern sphingolipid homeostasis in the human associated yeast Candida albicans. Cell Reports 30: 620-629
  Moreno-Velásquez SD, Tint SH, del Olmo Toledo V, Torsin S, De S, Pérez JC