Evolution of drug resistance in experimental populations of Candida albicans

Details

Serval ID
serval:BIB_E36FF09EB027
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evolution of drug resistance in experimental populations of Candida albicans
Journal
Journal of Bacteriology
Author(s)
Cowen  L. E., Sanglard  D., Calabrese  D., Sirjusingh  C., Anderson  J. B., Kohn  L. M.
ISSN
0021-9193 (Print)
Publication state
Published
Issued date
03/2000
Volume
182
Number
6
Pages
1515-22
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar
Abstract
Adaptation to inhibitory concentrations of the antifungal agent fluconazole was monitored in replicated experimental populations founded from a single, drug-sensitive cell of the yeast Candida albicans and reared over 330 generations. The concentration of fluconazole was maintained at twice the MIC in six populations; no fluconazole was added to another six populations. All six replicate populations grown with fluconazole adapted to the presence of drug as indicated by an increase in MIC; none of the six populations grown without fluconazole showed any change in MIC. In all populations evolved with drug, increased fluconazole resistance was accompanied by increased resistance to ketoconazole and itraconazole; these populations contained ergosterol in their cell membranes and were amphotericin sensitive. The increase in fluconazole MIC in the six populations evolved with drug followed different trajectories, and these populations achieved different levels of resistance, with distinct overexpression patterns of four genes involved in azole resistance: the ATP-binding cassette transporter genes, CDR1 and CDR2; the gene encoding the target enzyme of the azoles in the ergosterol biosynthetic pathway, ERG11; and the major facilitator gene, MDR1. Selective sweeps in these populations were accompanied by additional genomic changes with no known relationship to drug resistance: loss of heterozygosity in two of the five marker genes assayed and alterations in DNA fingerprints and electrophoretic karyotypes. These results show that chance, in the form of mutations that confer an adaptive advantage, is a determinant in the evolution of azole drug resistance in experimental populations of C. albicans.
Keywords
AIDS-Related Opportunistic Infections/microbiology Antifungal Agents/*pharmacology Candida albicans/*drug effects/*genetics/growth & development/isolation & purification Candidiasis, Oral/microbiology Colony Count, Microbial Culture Media DNA Fingerprinting Drug Resistance, Microbial/genetics *Evolution, Molecular Fluconazole/*pharmacology Humans Karyotyping Loss of Heterozygosity Microbial Sensitivity Tests Sequence Analysis, DNA
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:40
Last modification date
20/08/2019 16:07
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