title: Portrait of Candida albicans adherence regulators.
abstract: Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Finkel
authors.forename: Wenjie
authors.initials: W
authors.lastname: Xu
authors.forename: David
authors.initials: D
authors.lastname: Huang
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Hill
authors.forename: Jigar V
authors.initials: JV
authors.lastname: Desai
authors.forename: Carol A
authors.initials: CA
authors.lastname: Woolford
authors.forename: Jeniel E
authors.initials: JE
authors.lastname: Nett
authors.forename: Heather
authors.initials: H
authors.lastname: Taff
authors.forename: Carmelle T
authors.initials: CT
authors.lastname: Norice
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
authors.forename: Frederick
authors.initials: F
authors.lastname: Lanni
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
mesh_terms: D018441:Biofilms / Q000254:growth & development; D002176:Candida albicans / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D005800:Genes, Fungal
chemical_list: D005656:Fungal Proteins