Previous Article | Next Article 
Eukaryotic Cell, August 2009, p. 1197-1217, Vol. 8, No. 8
1535-9778/09/$08.00+0 doi:10.1128/EC.00120-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Remodeling of Global Transcription Patterns of Cryptococcus neoformans Genes Mediated by the Stress-Activated HOG Signaling Pathways 
,
Young-Joon Ko,1,
Yeong Man Yu,2,
Gyu-Bum Kim,1
Gir-Won Lee,1
Pil Jae Maeng,2
Sangsoo Kim,1
Anna Floyd,3
Joseph Heitman,3 and
Yong-Sun Bahn4*
Department of Bioinformatics and Life Science, Soongsil University, Seoul, South Korea,1 Department of Microbiology, Chungnam National University, Daejeon, South Korea,2 Departments of Molecular Genetics and Microbiology, Medicine, and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710,3 Department of Biotechnology, Center for Fungal Pathogenesis, Yonsei University, Seoul, South Korea4
Received 26 April 2009/ Accepted 11 June 2009
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 elucidate 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 encode a sodium/potassium efflux pump, protein kinase, multidrug transporter system, and elements of the ubiquitin-dependent system.
* Corresponding author. Mailing address: Department of Biotechnology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, 120-749, Seoul, Korea. Phone: 82-2-2123-5558. Fax: 82-2-362-7265. E-mail: ysbahn{at}yonsei.ac.kr
Published ahead of print on 19 June 2009.
Supplemental material for this article may be found at http://ec.asm.org/.
Y.-J. Ko and Y. M. Yu contributed equally to this work.
Eukaryotic Cell, August 2009, p. 1197-1217, Vol. 8, No. 8
1535-9778/09/$08.00+0 doi:10.1128/EC.00120-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»