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. 2020 Mar 24;64(4):e01651-19.
doi: 10.1128/AAC.01651-19. Print 2020 Mar 24.

Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration

Elisabete Ricardo  1   2 , Fréderic Grenouillet  3   4 , Isabel M Miranda  5   6 , Raquel M Silva  7 , Guilluame Eglin  3 , Nadège Devillard  8 , Acácio Gonçalves Rodrigues  5   2   9 , Cidália Pina-Vaz  5   2
Affiliations

Mechanisms of Acquired In Vivo and In Vitro Resistance to Voriconazole by Candida krusei following Exposure to Suboptimal Drug Concentration

Elisabete Ricardo et al. Antimicrob Agents Chemother. .

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.

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Figures

FIG 1
FIG 1
In vivo induction of resistance to voriconazole. (a) Timeline of the renal transplant procedure and antifungal therapy; identity of the C. krusei clinical isolates recovered from the kidney-transplant recipient and their respective susceptibility profiles. (b) Genotyping of C. krusei clinical isolates. M, molecular weight marker. (c) Relative gene expression profile of ABC1, ABC2, and ERG11 genes for the C. krusei clinical isolates. *, P ≤ 0.05.
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