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Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata.

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Title: Role of the Slt2 mitogen-activated protein kinase pathway in cell wall integrity and virulence in Candida glabrata.
Authors: Miyazaki, Taiga / Inamine, Tatsuo / Yamauchi, Shunsuke / Nagayoshi, Yosuke / Saijo, Tomomi / Izumikawa, Koichi / Seki, Masafumi / Kakeya, Hiroshi / Yamamoto, Yoshihiro / Yanagihara, Katsunori / Miyazaki, Yoshitsugu / Kohno, Shigeru
Issue Date: May-2010
Publisher: Blackwell Publishing Ltd.
Citation: FEMS yeast research, 10(3), pp.343-352; 2010
Abstract: Abstract The Slt2 mitogen-activated protein kinase pathway plays a major role in maintaining fungal cell wall integrity. In this study, we investigated the effects of SLT2 deletion and overexpression on drug susceptibility and virulence in the opportunistic fungal pathogen Candida glabrata. While the Deltaslt2 strain showed decreased tolerance to elevated temperature and cell wall-damaging agents, the SLT2-overexpressing strain exhibited increased tolerance to these stresses. A mutant lacking Rlm1, a transcription factor downstream of Slt2, displayed a cell wall-associated phenotype intermediate to that of the Deltaslt2 strain. When RLM1 was overexpressed, micafungin tolerance was increased in the wild-type strain and partial restoration of the drug tolerance was observed in the Deltaslt2 background. It was also demonstrated that echinocandin-class antifungals were more effective against C. glabrata under acidic conditions or when used concurrently with the chitin synthesis inhibitor nikkomycin Z. Finally, in a mouse model of disseminated candidiasis, the deletion and overexpression of C. glabrata SLT2 resulted in mild decreases and increases, respectively, in the CFUs from murine organs compared with the wild-type strain. These fundamental data will help in further understanding the mechanisms of cell wall stress response in C. glabrata and developing more effective treatments using echinocandin antifungals in clinical settings.
Keywords: Candida glabrata / Cell wall integrity / Echinocandin / MAPK pathway / PH / SLT2
URI: http://hdl.handle.net/10069/25190
ISSN: 15671356
DOI: 10.1111/j.1567-1364.2010.00611.x
PubMed ID: 20214686
Rights: © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved / The definitive version is available at www.blackwell-synergy.com
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/25190

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