title: Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2.
abstract: The Candida albicans RHR2 gene, which specifies a glycerol biosynthetic enzyme, is required for biofilm formation in vitro and in vivo. Prior studies indicate that RHR2 is ultimately required for expression of adhesin genes, such as ALS1. In fact, RHR2 is unnecessary for biofilm formation when ALS1 is overexpressed from an RHR2-independent promoter. Here, we describe two additional biological processes that depend upon RHR2: invasion into an abiotic substrate and pathogenicity in an abdominal infection model. We report here that abiotic substrate invasion occurs concomitantly with biofilm formation, and a screen of transcription factor mutants indicates that biofilm and hyphal formation ability correlates with invasion ability. However, analysis presented here of the rhr2Δ/Δ mutant separates biofilm formation and invasion. We found that an rhr2Δ/Δ mutant forms a biofilm upon overexpression of the adhesin gene ALS1 or the transcription factor genes BRG1 or UME6. However, the biofilm-forming strains do not invade the substrate. These results indicate that RHR2 has an adhesin-independent role in substrate invasion, and mathematical modeling argues that RHR2 is required to generate turgor. Previous studies have shown that abdominal infection by C. albicans has two aspects: infection of abdominal organs and persistence in abscesses. We report here that an rhr2Δ/Δ mutant is defective in both of these infection phenotypes. We find here that overexpression of ALS1 in the mutant restores infection of organs, but does not improve persistence in abscesses. Therefore, RHR2 has an adhesin-independent role in abdominal infection, just as it does in substrate invasion. This report suggests that RHR2, through glycerol synthesis, coordinates adherence with host- or substrate-interaction activities that enable proliferation of the C. albicans population.
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 289), Pittsburgh, PA 15213, USA. jigarvdesai@gmail.com.
authors.forename: Jigar V
authors.initials: JV
authors.lastname: Desai
authors.affiliation: Department of Medicine, Infectious Disease Division, University of Pittsburgh, 3550 Terrace Street, Scaife S869, Pittsburgh, PA 15261, USA. sjc43@pitt.edu.
authors.forename: Shaoji
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 289), Pittsburgh, PA 15213, USA. tammythinks@gmail.com.
authors.forename: Tammy
authors.initials: T
authors.lastname: Ying
authors.affiliation: Department of Medicine, Infectious Disease Division, University of Pittsburgh, 3550 Fifth Ave, Suite 872 Scaife Hall, Pittsburgh, PA 15261, USA. mhn5@pitt.edu.
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. cjc76@pitt.edu.|Infectious Diseases Section, VA Pittsburgh Healthcare System, 3550 Fifth Ave, Suite 867 Scaife Hall, Pittsburgh, PA 15261, USA. cjc76@pitt.edu.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 294C), Pittsburgh, PA 15213, USA. lanni@andrew.cmu.edu.
authors.forename: Frederick
authors.initials: F
authors.lastname: Lanni
authors.affiliation: Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 200B), Pittsburgh, PA 15213, USA. apm1@cmu.edu.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
keywords: Candida albicans; adherence; adhesin; biofilm; glycerol; infection; intra-abdominal candidiasis; invasion; turgor