title: Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit.
abstract: Systemic, life-threatening infections in humans are often caused by bacterial or fungal species that normally inhabit a different locale in our body, particularly mucosal surfaces. A hallmark of these opportunistic pathogens, therefore, is their ability to thrive in disparate niches within the host. In this work, we investigate the transcriptional circuitry and gene repertoire that enable the human opportunistic fungal pathogen Candida albicans to proliferate in two different niches. By screening a library of transcription regulator deletion strains in mouse models of intestinal colonization and systemic infection, we identified eight transcription regulators that play roles in at least one of these models. Using genome-wide chromatin immunoprecipitation, we uncovered a network comprising ∼800 target genes and a tightly knit transcriptional regulatory circuit at its core. The network is enriched with genes upregulated in C. albicans cells growing in the host. Our findings indicate that many aspects of commensalism and pathogenicity are intertwined and that the ability of this microorganism to colonize multiple niches relies on a large, integrated circuit.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, United States of America. jperez@ucsf.edu
authors.forename: J Christian
authors.initials: JC
authors.lastname: Pérez
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kumamoto
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D002177:Candidiasis / Q000235:genetics / Q000382:microbiology; D005260:Female; D005656:Fungal Proteins; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors