Genome-wide expression profiling of the response to short-term exposure to fluconazole in Cryptococcus neoformans serotype A

BMC Microbiology

Research Article

Dominique Sanglard¹  Selene Ferrari¹  Brunella Posteraro²  Elena De Carolis²  Riccardo Torelli²  Giovanni Fadda²  Maurizio Sanguinetti²  Ada Rita Florio² 

[1] Institute of Microbiology, University of Lausanne and University Hospital Center, Lausanne, Rue du Bugnon 48, CH-1011, Lausanne, Switzerland;Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168, Rome, Italy;

关键词: Azole;    Ergosterol;    Caspofungin;    Cryptococcosis;    Cryptococcal Meningitis;   

DOI  :  10.1186/1471-2180-11-97

 received in 2010-12-22, accepted in 2011-05-11,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundFluconazole (FLC), a triazole antifungal drug, is widely used for the maintenance therapy of cryptococcal meningoencephalitis, the most common opportunistic infection in AIDS patients. In this study, we examined changes in the gene expression profile of the C. neoformans reference strain H99 (serotype A) following FLC treatment in order to investigate the adaptive cellular responses to drug stress.ResultsSimultaneous analysis of over 6823 transcripts revealed that 476 genes were responsive to FLC. As expected up-regulation of genes involved in ergosterol biosynthesis was observed, including the azole target gene ERG11 and ERG13, ERG1, ERG7, ERG25, ERG2, ERG3 and ERG5. In addition, SRE1 which is a gene encoding a well-known regulator of sterol homeostasis in C. neoformans was up-regulated. Several other genes such as those involved in a variety of important cellular processes (i.e. lipid and fatty acid metabolism, cell wall maintenance, stress and virulence) were found to be up-regulated in response to FLC treatment. Conversely, expression of AFR1, the major transporter of azoles in C. neoformans, was not regulated by FLC.ConclusionsShort-term exposure of C. neoformans to FLC resulted in a complex altered gene expression profile. Some of the observed changes could represent specific adaptive responses to the antifungal agent in this pathogenic yeast.

【 授权许可】

Unknown   
© Florio et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.