The DOI matches its Crossref record; 33 of the 34 references it cites were found in a registry or an index.
Evolution of Drug Resistance in Experimental Populations of Candida albicans
Open accessAbstract
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.
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In the citing paper
“Selective sweeps in response to drug selection are also observed in experimental populations of C. albicans during the evolution of azole resistance in vitro [107].”
From Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata (2012) · cites this paper as [107]
In the citing paper
“The impact of drug concentration on the spectrum and effect of mutations acquired during adaptation is not known for any fungal pathogen, and how the specific level of a given stress influences the distribution of beneficial mutations has been poorly explored in general.”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans (2023) · cites this paper as Cowen et al. 2000
In the citing paper
“Overall, the impact of genetic and environmental factors, including FLC concentration, on the acquisition of drug resistance and tolerance phenotypes is not known.”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans (2023) · cites this paper as Cowen et al. 2000
In the citing paper
“In one example, six lineages from one C. albicans strain were maintained at increasing concentrations of FLC for 300–400 generations, where the MIC50 was quantified every 10–20 generations and the drug concentration was increased to twice the MIC50, to a maximum concentration of 128 μg/ml FLC (Cowen et al. 2000).”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans (2023) · cites this paper as Cowen et al. 2000
In the citing paper
“Prior studies into how antifungal drugs impact the spectrum of mutations observed during adaption primarily focused on increasing FLC concentrations or on short-term evolution experiments in a single concentration of FLC (Cowen et al. 2000; Anderson et al. 2003; Mount et al. 2018; Rybak et al. 2020; Burrack et al. 2022).”
From Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in Candida albicans (2023) · cites this paper as Cowen et al. 2000
In the citing paper
“For example, Cowen et al. [150] serially propagated six experimental populations of C. albicans derived from a single colony for 330 generations in medium supplemented with fluconazole at a concentration doubling their MIC.”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [150]
In the citing paper
“Both methods have been successfully used to study the emergence of drug resistance in Candida yeasts [150,151].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [150]
In the citing paper
“Loss of heterozygosity at gene loci of isolates serially passaged in azole-containing media, as well as laboratory strains passaged through mice models of haematogenously disseminated disease, both suggest that significant genetic rearrangements take place as a result of host and drug stress.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans (2020) · cites this paper as [152]
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Cited by
Sorted by citations
Evolution Experiments with Microorganisms: The Dynamics and Genetic Bases of Adaptation
Elena, S. F., & Lenski, R. E. (2003) · Nature Reviews Genetics · doi:10.1038/nrg1088 · Cited by 1,386
The Evolution of Transcriptional Regulation in Eukaryotes
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Aneuploidy and Isochromosome Formation in Drug-Resistant Candida albicans
Selmecki, A., Forche, A., & Berman, J. (2006) · Science · doi:10.1126/science.1128242 · Cited by 733
The Evolution of Fungicide Resistance
Lucas, J. A., Hawkins, N. J., & FRAAIJE, B. A. (2014) · Advances in applied microbiology · doi:10.1016/bs.aambs.2014.09.001 · Cited by 652
Regulatory circuitry governing fungal development, drug resistance, and disease.
Shapiro, R. S., Robbins, N., & Cowen, L. E. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00045-10 · Cited by 576
Self-citation
Metadata
- Authors
- Cowen, L. E., Sanglard, D., Calabrese, D., Sirjusingh, C., Anderson, J. B., & Kohn, L. M.
- Affiliations
- University of Toronto (CA)
- Centre Hospitalier Universitaire Vaudois (CH)
- Venue
- Journal of Bacteriology
- Publisher
- American Society for Microbiology
- Published
- 2000-03-15
- Volume
- 182
- Issue
- 6
- Pages
- 1515-1522
- ISSN
- 0021-9193 (ISSN-L)
- 1098-5530
- PMC
- PMC94447
- OpenAlex
- W1973285175
- Cited by
- 207
- References
- 34
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 9
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Bacteriology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Pfizer
- Pfizer Canada
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- Candida albicans, fluconazole resistance, experimental evolution, antifungal resistance, ketoconazole, itraconazole, CDR1, CDR2, ERG11, MDR1, ABC transporters, selective sweeps, loss of heterozygosity, karyotype changes, DNA fingerprinting, minimum inhibitory concentration
- MeSH terms
- Antifungal Agents, Candida albicans, Candidiasis, Oral, Culture Media, Drug Resistance, Microbial, Humans, Karyotyping, Microbial Sensitivity Tests, Colony Count, Microbial, Fluconazole, DNA Fingerprinting, AIDS-Related Opportunistic Infections, Sequence Analysis, DNA, Evolution, Molecular, Loss of Heterozygosity
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