title: Genome-wide expression profiling of the response to short-term exposure to fluconazole in Cryptococcus neoformans serotype A.
abstract: BACKGROUND
  Fluconazole (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.
  
  
  RESULTS
  Simultaneous 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.
  
  
  CONCLUSIONS
  Short-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.
authors.affiliation: Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.
authors.forename: Ada Rita
authors.initials: AR
authors.lastname: Florio
authors.forename: Selene
authors.initials: S
authors.lastname: Ferrari
authors.forename: Elena
authors.initials: E
authors.lastname: De Carolis
authors.forename: Riccardo
authors.initials: R
authors.lastname: Torelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fadda
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sanguinetti
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.forename: Brunella
authors.initials: B
authors.lastname: Posteraro
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D015725:Fluconazole / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D013312:Stress, Physiological
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole