title: Characterization of theCandida albicansAmino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is anS-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis.
abstract: Amino acids are key sources of nitrogen for growth ofCandida albicans. In order to detect and take up these amino acids from a broad range of different and changing nitrogen sources inside the host, this fungus must be able to adapt via its expression of genes for amino acid uptake and further metabolism. We analyzed sixC. albicansputative general amino acid permeases based on their homology to theSaccharomyces cerevisiaeGap1 general amino acid permease. We generated single- and multiple-deletion strains and found that, based on growth assays and transcriptional or posttranscriptional regulation, Gap2 is the functional orthologue toScGap1, with broad substrate specificity. Expression analysis showed that expression of allGAPgenes is under control of the Csy1 amino acid sensor, which is different from the situation inS. cerevisiae, where the expression ofScGAP1is not regulated by Ssy1. We show that Gap4 is the functional orthologue ofScSam3, the onlyS-adenosylmethionine (SAM) transporter inS. cerevisiae, and we report that Gap4 is required for SAM-induced morphogenesis.IMPORTANCECandida albicansis a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that theC. albicansgenome encodes 6 orthologues of theSaccharomyces. cerevisiaegeneral amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show thatC. albicansGap2 is the functional orthologue ofScGap1 and thatC. albicansGap4 is an orthologue ofScSam3, anS-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor ofC. albicans.
authors.affiliation: VIB Department of Molecular Microbiology, KU Leuven, Flanders, Belgium; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium; Department of Membrane Transport, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Kraidlova
authors.affiliation: VIB Department of Molecular Microbiology, KU Leuven, Flanders, Belgium; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Sanne
authors.initials: S
authors.lastname: Schrevens
authors.affiliation: VIB Department of Molecular Microbiology, KU Leuven, Flanders, Belgium; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Tournu
authors.affiliation: VIB Department of Molecular Microbiology, KU Leuven, Flanders, Belgium; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Griet
authors.initials: G
authors.lastname: Van Zeebroeck
authors.affiliation: Department of Membrane Transport, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Sychrova
authors.affiliation: VIB Department of Molecular Microbiology, KU Leuven, Flanders, Belgium; Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Leuven, Belgium.
authors.forename: Patrick
authors.identifier: 0000-0002-1542-897X
authors.initials: P
authors.lastname: Van Dijck
keywords: Candida albicans; GAP1; S-adenosyl methionine; general amino acid permease; morphogenesis