Methionine is required for cAMP‐PKA‐mediated morphogenesis and virulence of <i>Candida albicans</i>
-
- Sanne Schrevens
- VIB – KU Leuven Center for Microbiology Leuven 3001 Belgium
-
- Griet Van Zeebroeck
- VIB – KU Leuven Center for Microbiology Leuven 3001 Belgium
-
- Michael Riedelberger
- Medical University of Vienna, Center of Medical Biochemistry, Max F. Perutz Laboratories, Campus Vienna Biocenter Vienna Austria
-
- Hélène Tournu
- VIB – KU Leuven Center for Microbiology Leuven 3001 Belgium
-
- Karl Kuchler
- Medical University of Vienna, Center of Medical Biochemistry, Max F. Perutz Laboratories, Campus Vienna Biocenter Vienna Austria
-
- Patrick Van Dijck
- VIB – KU Leuven Center for Microbiology Leuven 3001 Belgium
説明
<jats:title>Summary</jats:title><jats:p><jats:italic>Candida albicans</jats:italic> is a major human fungal pathogen, causing superficial, as well as life‐threatening invasive infections. Therefore, it has to adequately sense and respond to the host defense by expressing appropriate virulence attributes. The most important virulence factor of <jats:italic>C. albicans</jats:italic> is the yeast‐to‐hyphae morphogenetic switch, which can be induced by numerous environmental cues, including the amino acid methionine. Here, we show an essential role for methionine permease Mup1 in methionine‐induced morphogenesis, biofilm formation, survival inside macrophages and virulence. Furthermore, we demonstrate that this process requires conversion of methionine into <jats:italic>S</jats:italic>‐adenosyl methionine (SAM) and its decarboxylation by Spe2. The resulting amino‐propyl group is then used for biosynthesis of polyamines, which have been shown to activate adenylate cyclase. Inhibition of the <jats:italic>SPE2</jats:italic> SAM decarboxylase gene strongly impairs methionine‐induced morphogenesis on specific media and significantly delays virulence in the mouse systemic infection model system. Further proof of the connection between methionine uptake and initial metabolism and the cAMP‐PKA pathway was obtained by showing that both Mup1 and Spe2 are required for cAMP production in response to methionine. Our results suggest that amino acid transport and further metabolism are interesting therapeutic targets as inhibitors of this may prevent the morphogenetic switch, thereby preventing virulence.</jats:p>
収録刊行物
-
- Molecular Microbiology
-
Molecular Microbiology 108 (3), 258-275, 2018-03-06
Wiley