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Quantitative proteomics and metabolomics approaches to demonstrate N-acetyl-D-glucosamine inducible amino acid deprivation response as morphological switch in Candida albicans

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Title Quantitative proteomics and metabolomics approaches to demonstrate N-acetyl-D-glucosamine inducible amino acid deprivation response as morphological switch in Candida albicans
 
Creator Kamthan, Mohan
Mukhopadhyay, Gauranga
Chakraborty, Niranjan
Chakraborty, Subhra
Datta, Asis
 
Subject Candida
Morphogenesis
GlcNAc
Leloir pathway
GCN response
 
Description Candida albicans is a life threatening polymorphic pathogen for immunocompromised patients, causing superficial as well as invasive systemic diseases. The mucosal membranes of the host, which are the primary sites of its infection, are rich in amino sugars like N-acetylglucosamine (GlcNAc). GlcNAc is also one of the potent inducers of morphological transition, an important pathogenic trait of C. albicans. We thus performed proteomic analysis on total soluble proteins to identify the molecules involved in this response. Proteomic analysis using 2-DE demonstrated reproducible upregulation of 36 spots from a total of 585 matched spots. Mass spectroscopy (MS/MS) analyses of upregulated proteins revealed that carbohydrate and amino acid metabolism were the most prominent functional classes. Metabolite profiling using GC-MS allowed a quantitative comparison of 58 metabolites in GlcNAc or glucose grown cells. We observed a significant decrease in the intracellular amino acid pool of GlcNAc grown cells. Moreover, GlcNAc induces both bZIP transcription factor (GCN4) and eIF2α kinase (GCN2) which are responsible for the activation of general amino acid control response in C. albicans. Inactivation of these genes blocks GlcNAc induced morphogenesis. Altogether these results suggest that amino acid starvation is the morphogenetic signal in presence of GlcNAc in C. albicans.
This work was supported by the Department of Biotechnology, Ministry of Science and Technology, Government of India.
 
Date 2014-05-15T10:20:13Z
2014-05-15T10:20:13Z
2012
20 February 2012
 
Type Article
 
Identifier Fungal Genet. Biol., 49(5): 369-378
http://hdl.handle.net/123456789/243
 
Language en
 
Publisher Elsevier