Drug resistance genes and trailing growth in Candida albicans isolates

J Antimicrob Chemother. 2004 Feb;53(2):217-24. doi: 10.1093/jac/dkh040. Epub 2003 Dec 19.


Objectives: To investigate possible molecular mechanisms of azole resistance among fluconazole-susceptible bloodstream isolates of Candida albicans that displayed the trailing growth phenomenon, and to compare these isolates with bloodstream and mucosal isolates that showed reduced susceptibilities to fluconazole.

Methods: Twelve C. albicans isolates-seven trailing and five susceptible dose dependent (SDD) or resistant (R)-were screened for ERG11 mutations by DNA sequencing and quantification of ERG11, CDR1 and MDR1 expression by RT-PCR using the LightCycler high-speed PCR system.

Results: SDD and R isolates possessed more homozygous ERG11 mutations than did the trailing isolates. Two of these, V404I and V509M, have not been described previously and were found exclusively in fluconazole SDD and R isolates. Quantification of ERG11 expression revealed that both trailing and SDD and R isolates were capable of ERG11 up-regulation in response to fluconazole, although the SDD and R isolates showed maximal up-regulation at higher fluconazole concentrations. Quantification of CDR1 and MDR1 revealed that all isolates, regardless of in vitro fluconazole response, were capable of CDR1 and MDR1 up-regulation following fluconazole exposure. Furthermore, the SDD and R isolates expressed higher constitutive levels of CDR1 and MDR1 or CDR1, respectively, in the absence of drug compared with trailing isolates.

Conclusions: Trailing isolates, although susceptible to fluconazole, express the same molecular mechanisms as SDD and R isolates following fluconazole exposure but regulate them differently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Azoles / pharmacology
  • Candida albicans / drug effects*
  • Candida albicans / genetics*
  • Candida albicans / growth & development
  • Candidiasis / microbiology*
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • DNA, Fungal / genetics
  • Drug Resistance, Fungal / genetics*
  • Fluconazole / pharmacology
  • Genes, Fungal / genetics
  • Genes, MDR / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Point Mutation / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sterols / chemistry
  • Transcription, Genetic / genetics


  • Antifungal Agents
  • Azoles
  • DNA, Complementary
  • DNA, Fungal
  • Sterols
  • Fluconazole