EC Accepts, published online ahead of print on 19 June 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Ko, Y.-J. Articles by Bahn, Y.-S. PubMed PubMed Citation Articles by Ko, Y.-J. Articles by Bahn, Y.-S.

 Previous Article  |  Next Article 

Eukaryotic Cell doi:10.1128/EC.00120-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Remodeling of global transcription patterns of Cryptococcus neoformans genes mediated by the stress-activated HOG signaling pathways

Young-Joon Ko, Yeong Man Yu, Gyu-Bum Kim, Gir-Won Lee, Pil Jae Maeng, Sang-Soo Kim, Anna Floyd, Joseph Heitman, and Yong-Sun Bahn^*

Department of Bioinformatics and Life Science, Soongsil University, Seoul, Korea; Department of Microbiology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea; Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710; Department of Biotechnology, Center for Fungal Pathogenesis, College of Life Science and Biotechnology, Yonsei University Seoul, Korea

^* To whom correspondence should be addressed. Email: ysbahn{at}yonsei.ac.kr.

The ability to sense and adapt to a hostile host environment is a crucial element for virulence of pathogenic fungi, including Cryptococcus neoformans. These cellular responses are evoked by diverse signaling cascades, including the stress-activated HOG pathway. Despite previous analysis of central components of the HOG pathway, its downstream signaling network is poorly characterized in C. neoformans. Here we performed comparative transcriptome analysis with HOG signaling mutants to explore stress-regulated genes and their correlation with the HOG pathway in C. neoformans. In this study we not only provide important insights into remodeling patterns of global gene expression for counteracting external stresses, but also elucidated novel characteristics of the HOG pathway in C. neoformans. First, inhibition of the HOG pathway increases expression of ergosterol biosynthesis genes and cellular ergosterol content, conferring a striking synergistic antifungal activity with amphotericin B and providing an excellent opportunity to develop a novel therapeutic method for treatment of cryptococcosis. Second, a number of cadmium-sensitive genes are differentially regulated by the HOG pathway, and their mutation causes resistance to cadmium. Finally, we have discovered novel stress-defense and HOG-dependent genes, which encodes a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system.