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Methionine is required for cAMP-PKA-mediated morphogenesis and virulence of Candida albicans.
Schrevens, Sanne; Van Zeebroeck, Griet; Riedelberger, Michael; Tournu, Hélène; Kuchler, Karl; Van Dijck, Patrick.
Afiliação
  • Schrevens S; VIB - KU Leuven Center for Microbiology, Leuven 3001, Belgium.
  • Van Zeebroeck G; Laboratory of Molecular Cell Biology, KU Leuven, Leuven 3001, Belgium.
  • Riedelberger M; VIB - KU Leuven Center for Microbiology, Leuven 3001, Belgium.
  • Tournu H; Laboratory of Molecular Cell Biology, KU Leuven, Leuven 3001, Belgium.
  • Kuchler K; Medical University of Vienna, Center of Medical Biochemistry, Max F. Perutz Laboratories, Campus Vienna Biocenter, Vienna, Austria.
  • Van Dijck P; VIB - KU Leuven Center for Microbiology, Leuven 3001, Belgium.
Mol Microbiol ; 108(3): 258-275, 2018 05.
Article em En | MEDLINE | ID: mdl-29453849
ABSTRACT
Candida albicans 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 C. albicans 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 S-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 SPE2 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Candida albicans / Metionina Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Candida albicans / Metionina Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article