title: Effects of fluconazole treatment of mice infected with fluconazole-susceptible and -resistant Candida tropicalis on fungal cell surface hydrophobicity, adhesion and biofilm formation.
abstract: BACKGROUND
  The incidence of Candida tropicalis less susceptible to fluconazole (FLC) has been reported in many parts of the world.
  
  
  OBJECTIVE
  The aim of this study was to examine the changes of putative virulence attributes of Candida tropicalis accompanying the development of resistance to FLC in vitro and in vivo.
  
  
  METHODS
  A FLC-resistant strain (FLC-R) was obtained after sequential exposure of a clinical isolate FLC-sensitive (FLC-S) to increasing concentrations of the antifungal. The course of infection by both strains was analyzed in BALB/c mice. Analyses of gene expression were performed by real-time polymerase chain reaction PCR. The cell surface hydrophobicity, adhesion and biofilm formation were also determined.
  
  
  RESULTS
  Development of resistance to FLC could be observed after 15 days of subculture in azole-containing medium. Overexpression of MDR1 and ERG11 genes were observed in FLC-R, and this strain exhibited enhanced virulence in mice, as assessed by the mortality rate. All mice challenged with the FLC-R died and FLC-treatment caused earlier death in mice infected with this strain. All animals challenged with FLC-S survived the experiment, regardless of FLC-treatment. Overall, FLC-R derivatives strains were significantly more hydrophobic than FLC-S strains and showed greater adherence and higher capacity to form biofilm on polystyrene surface.
  
  
  CONCLUSIONS
  The expression of virulence factors was higher in FLC-R-C. tropicalis and it was enhanced after FLC-exposure. These data alert us to the importance of identifying microorganisms that show resistance to the antifungals to establish an appropriate management of candidiasis therapy.
authors: R L
authors: RL
authors: Kanoshiki
authors: S B
authors: SB
authors: de Paula
authors: J P
authors: JP
authors: Santos
authors: A T
authors: AT
authors: Morey
authors: N B
authors: NB
authors: Souza
authors: L M
authors: LM
authors: Yamauchi
authors: B P
authors: BP
authors: Dias Filho
authors: Department of Microbiology, Biological Sciences Center, State University of Londrina, Londrina, Brazil.
authors: S F
authors: SF
authors: Yamada-Ogatta
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms; D041022:Candida tropicalis / Q000187:drug effects* / Q000502:physiology*; D002177:Candidiasis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D002462:Cell Membrane / Q000737:chemistry; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole