Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration
- PMID: 31932372
- PMCID: PMC7179295
- DOI: 10.1128/AAC.01651-19
Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration
Abstract
Five Candida krusei isolates (susceptible and resistant) recovered from the urine of a kidney transplant patient treated with voriconazole (VRC) 200 mg twice daily for 20 days were studied. Eight unrelated clinical isolates of C. krusei were exposed in vitro to VRC 0.001 μg/ml for 30 days. Development of VRC transient resistance occurred in vivo, and induction of permanent resistance occurred in vitro Mostly, ABC1 and ERG11 genes were overexpressed, and a homozygous T418C mutation in the ERG11 gene was found.
Keywords: ABC1 ABC2 efflux pump genes; Candida krusei; ERG11 gene mutations; candidiasis; candiduria; mechanisms of antifungal resistance; underexposure to antifungal drugs; voriconazole.
Copyright © 2020 American Society for Microbiology.
Figures

Similar articles
-
In vivo and in vitro acquisition of resistance to voriconazole by Candida krusei.Antimicrob Agents Chemother. 2014 Aug;58(8):4604-11. doi: 10.1128/AAC.02603-14. Epub 2014 May 27. Antimicrob Agents Chemother. 2014. PMID: 24867987 Free PMC article.
-
Overexpression of Both ERG11 and ABC2 Genes Might Be Responsible for Itraconazole Resistance in Clinical Isolates of Candida krusei.PLoS One. 2015 Aug 26;10(8):e0136185. doi: 10.1371/journal.pone.0136185. eCollection 2015. PLoS One. 2015. PMID: 26308936 Free PMC article.
-
Mutations and/or Overexpressions of ERG4 and ERG11 Genes in Clinical Azoles-Resistant Isolates of Candida albicans.Microb Drug Resist. 2017 Jul;23(5):563-570. doi: 10.1089/mdr.2016.0095. Epub 2016 Dec 15. Microb Drug Resist. 2017. PMID: 27976986
-
Resistance in human pathogenic yeasts and filamentous fungi: prevalence, underlying molecular mechanisms and link to the use of antifungals in humans and the environment.Dan Med J. 2016 Oct;63(10):B5288. Dan Med J. 2016. PMID: 27697142 Review.
-
Antifungal drug resistance in pathogenic fungi.Med Mycol. 1998;36 Suppl 1:119-28. Med Mycol. 1998. PMID: 9988500 Review.
Cited by
-
Unlocking the potential of experimental evolution to study drug resistance in pathogenic fungi.NPJ Antimicrob Resist. 2024 Dec 12;2(1):48. doi: 10.1038/s44259-024-00064-1. NPJ Antimicrob Resist. 2024. PMID: 39843963 Free PMC article. Review.
-
Antifungal Activity and Mode of Action of Miltefosine Against Clinical Isolates of Candida krusei.Front Microbiol. 2020 May 19;11:854. doi: 10.3389/fmicb.2020.00854. eCollection 2020. Front Microbiol. 2020. PMID: 32508766 Free PMC article.
-
In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak.Antimicrob Agents Chemother. 2020 Oct 20;64(11):e01124-20. doi: 10.1128/AAC.01124-20. Print 2020 Oct 20. Antimicrob Agents Chemother. 2020. PMID: 32839219 Free PMC article.
-
Prevalence of Antifungal Resistance, Genetic Basis of Acquired Azole and Echinocandin Resistance, and Genotyping of Candida krusei Recovered from an International Collection.Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0185621. doi: 10.1128/AAC.01856-21. Epub 2021 Dec 6. Antimicrob Agents Chemother. 2022. PMID: 34871096 Free PMC article.
-
Biology and genetic diversity of Candida krusei isolates from fermented vegetables and clinical samples in China.Virulence. 2024 Dec;15(1):2411543. doi: 10.1080/21505594.2024.2411543. Epub 2024 Oct 17. Virulence. 2024. PMID: 39359062 Free PMC article.
References
-
- Bougnoux M-E, Kac G, Aegerter P, d'Enfert C, Fagon J-Y, CandiRea Study Group . 2008. Candidemia and candiduria in critically ill patients admitted to intensive care units in France: incidence, molecular diversity, management and outcome. Intensive Care Med 34:292–299. doi:10.1007/s00134-007-0865-y. - DOI - PubMed
-
- Brammer KW, Coakley AJ, Jezequel SG, Tarbit MH. 1991. The disposition and metabolism of [14C]fluconazole in humans. Drug Metab Dispos 19:764–767. - PubMed
Publication types
MeSH terms
Substances
Supplementary concepts
LinkOut - more resources
Full Text Sources
Medical