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Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: essential in C. glabrata, and essential for virulence in C. albicans.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: essential in C. glabrata, and essential for virulence in C. albicans.
 
Creator Yadav, Amit Kumar
Desai, Prashant Ramesh
Rai, Maruti Nandan
Kaur, Rupinder
Ganesan, K
Bachhawat, Anand K
 
Subject QR Microbiology
 
Description Redox pathways play a key role in pathogenesis. Glutathione, a central molecule in redox homeostasis in yeasts, is an essential metabolite, but its requirements can be met either from endogenous biosynthesis or from the extracellular milieu. In this report we have examined the importance of glutathione biosynthesis in two major human opportunistic fungal pathogens, Candida albicans and Candida glabrata. As the genome sequence of C. glabrata had suggested the absence of glutathione transporters, we initially investigated exogenous glutathione utilization in C. glabrata by disruption of the MET15 gene, involved in methionine biosynthesis. We observed an organic sulphur auxotrophy in a C. glabrata met15Δ strain; however, unlike its Saccharomyces cerevisiae counterpart, the C. glabrata met15Δ strain was unable to grow on exogenous glutathione. This inability to grow on exogenous glutathione was demonstrated to be due to the lack of a functional glutathione transporter, despite the presence of a functional glutathione degradation machinery (the Dug pathway). In the absence of the ability to obtain glutathione from the extracellular medium, we examined and could demonstrate that γ-glutamyl cysteine synthase, the first enzyme of glutathione biosynthesis, was essential in C. glabrata. Further, although γ-glutamyl cysteine synthase has been reported to be non-essential in C. albicans, we report here for what is believed to be the first time that the enzyme is required for survival in human macrophages in vitro, as well as for virulence in a murine model of disseminated candidiasis. The essentiality of γ-glutamyl cysteine synthase in C. glabrata, and its essentiality for virulence in C. albicans, make the enzyme a strong candidate for antifungal development.
 
Publisher Society for General Microbiology (SGM)
 
Date 2011-02
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/490/1/bachhawat11.pdf
Yadav, Amit Kumar and Desai, Prashant Ramesh and Rai, Maruti Nandan and Kaur, Rupinder and Ganesan, K and Bachhawat, Anand K (2011) Glutathione biosynthesis in the yeast pathogens Candida glabrata and Candida albicans: essential in C. glabrata, and essential for virulence in C. albicans. Microbiology (Reading, England), 157 (Pt 2). pp. 484-95. ISSN 1465-2080
 
Relation http://mic.sgmjournals.org/content/157/2/484.short#fn-1
http://crdd.osdd.net/open/490/