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Pathogens 2015, 4(3), 573-589; doi:10.3390/pathogens4030573

Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2

1
Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 289), Pittsburgh, PA 15213, USA
2
Department of Medicine, Infectious Disease Division, University of Pittsburgh, 3550 Terrace Street, Scaife S869, Pittsburgh, PA 15261, USA
3
Department of Medicine, Infectious Disease Division, University of Pittsburgh, 3550 Fifth Ave, Suite 872 Scaife Hall, Pittsburgh, PA 15261, USA
4
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
5
Infectious Diseases Section, VA Pittsburgh Healthcare System, 3550 Fifth Ave, Suite 867 Scaife Hall, Pittsburgh, PA 15261, USA
6
Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 294C), Pittsburgh, PA 15213, USA
7
Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave (MI- 200B), Pittsburgh, PA 15213, USA
Current Address: National Institutes of Health, Bldg 10, Room 11C116, 10 Center Drive, Bethesda, MD 20814, USA.
*
Author to whom correspondence should be addressed.
Academic Editor: Lawrence S. Young
Received: 13 June 2015 / Revised: 10 July 2015 / Accepted: 13 July 2015 / Published: 24 July 2015
(This article belongs to the Special Issue Candida Albicans Infections)
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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. View Full-Text
Keywords: Candida albicans; adherence; invasion; biofilm; intra-abdominal candidiasis; glycerol; turgor; infection; adhesin Candida albicans; adherence; invasion; biofilm; intra-abdominal candidiasis; glycerol; turgor; infection; adhesin
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Desai, J.V.; Cheng, S.; Ying, T.; Nguyen, M.H.; Clancy, C.J.; Lanni, F.; Mitchell, A.P. Coordination of Candida albicans Invasion and Infection Functions by Phosphoglycerol Phosphatase Rhr2. Pathogens 2015, 4, 573-589.

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