Mechanisms of acquired in vivo and in vitro resistance to voriconazole by Candida krusei following exposure to suboptimal drug concentration

Elisabete Ricardo; Fréderic Grenouillet; Isabel M. Miranda; Raquel M. Silva; Guilluame Eglin; Nadège Devillard; Acácio Gonçalves Rodrigues; Cidália Pina-Vaza

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

Elisabete Ricardo^*, Fréderic Grenouillet, Isabel M. Miranda, Raquel M. Silva, Guilluame Eglin, Nadège Devillard, Acácio Gonçalves Rodrigues, Cidália Pina-Vaza

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Article number	e01651-19
Number of pages	6
Journal	Antimicrobial Agents and Chemotherapy
Volume	64
Issue number	4
DOIs	https://doi.org/10.1128/AAC.01651-19
Publication status	Published - 2020

Keywords

ABC1 ABC2 efflux pump genes
Candida krusei
Candidiasis
Candiduria
ERG11 gene mutations
Mechanisms of antifungal resistance
Underexposure to antifungal drugs
Voriconazole

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Ricardo, E., Grenouillet, F., Miranda, I. M., Silva, R. M., Eglin, G., Devillard, N., Rodrigues, A. G., & Pina-Vaza, C. (2020). Mechanisms of acquired in vivo and in vitro resistance to voriconazole by Candida krusei following exposure to suboptimal drug concentration. Antimicrobial Agents and Chemotherapy, 64(4), Article e01651-19. https://doi.org/10.1128/AAC.01651-19

@article{0930a8b1f5be452483ce69e50597ca5b,

title = "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, Candidiasis, Candiduria, ERG11 gene mutations, Mechanisms of antifungal resistance, Underexposure to antifungal drugs, Voriconazole",

author = "Elisabete Ricardo and Fr{\'e}deric Grenouillet and Miranda, {Isabel M.} and Silva, {Raquel M.} and Guilluame Eglin and Nad{\`e}ge Devillard and Rodrigues, {Ac{\'a}cio Gon{\c c}alves} and Cid{\'a}lia Pina-Vaza",

note = "Funding Information: I.M.M. was supported by FCT (Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia) Ci{\^e}ncia 2008 and cofinanced by the European Social Fund. R.M.S. was partially funded by FEDER (Programa Operacional Factores de Competitividade-COMPETE) and by National Funds through FCT (projects UID/BIM/04501/2013 and POCI-01-0145-FEDER-007628 and grant SFRH/BPD/111148/2015). The remaining authors have no conflicts of interest to report. Funding Information: I.M.M. was supported by FCT (Funda??o para a Ci?ncia e a Tecnologia) Ci?ncia 2008 and cofinanced by the European Social Fund. R.M.S. was partially funded by FEDER (Programa Operacional Factores de Competitividade-COMPETE) and by National Funds through FCT (projects UID/BIM/04501/2013 and POCI-01-0145-FEDER-007628 and grant SFRH/BPD/111148/2015). The remaining authors have no conflicts of interest to report. Publisher Copyright: Copyright {\textcopyright} 2020 American Society for Microbiology. All Rights Reserved.",

year = "2020",

doi = "10.1128/AAC.01651-19",

language = "English",

volume = "64",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

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T1 - Mechanisms of acquired in vivo and in vitro resistance to voriconazole by Candida krusei following exposure to suboptimal drug concentration

AU - Ricardo, Elisabete

AU - Grenouillet, Fréderic

AU - Miranda, Isabel M.

AU - Silva, Raquel M.

AU - Eglin, Guilluame

AU - Devillard, Nadège

AU - Rodrigues, Acácio Gonçalves

AU - Pina-Vaza, Cidália

N1 - Funding Information: I.M.M. was supported by FCT (Fundação para a Ciência e a Tecnologia) Ciência 2008 and cofinanced by the European Social Fund. R.M.S. was partially funded by FEDER (Programa Operacional Factores de Competitividade-COMPETE) and by National Funds through FCT (projects UID/BIM/04501/2013 and POCI-01-0145-FEDER-007628 and grant SFRH/BPD/111148/2015). The remaining authors have no conflicts of interest to report. Funding Information: I.M.M. was supported by FCT (Funda??o para a Ci?ncia e a Tecnologia) Ci?ncia 2008 and cofinanced by the European Social Fund. R.M.S. was partially funded by FEDER (Programa Operacional Factores de Competitividade-COMPETE) and by National Funds through FCT (projects UID/BIM/04501/2013 and POCI-01-0145-FEDER-007628 and grant SFRH/BPD/111148/2015). The remaining authors have no conflicts of interest to report. Publisher Copyright: Copyright © 2020 American Society for Microbiology. All Rights Reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - ABC1 ABC2 efflux pump genes

KW - Candida krusei

KW - Candidiasis

KW - Candiduria

KW - ERG11 gene mutations

KW - Mechanisms of antifungal resistance

KW - Underexposure to antifungal drugs

KW - Voriconazole

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U2 - 10.1128/AAC.01651-19

DO - 10.1128/AAC.01651-19

M3 - Article

C2 - 31932372

AN - SCOPUS:85082394630

SN - 0066-4804

VL - 64

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 4

M1 - e01651-19

ER -

Mechanisms of acquired in vivo and in vitro resistance to voriconazole by Candida krusei following exposure to suboptimal drug concentration

Abstract

Keywords

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CIIS: Center for Interdisciplinary Research in Health

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Mechanisms of acquired in vivo and in vitro resistance to voriconazole by Candida krusei following exposure to suboptimal drug concentration

Abstract

Keywords

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CIIS: Center for Interdisciplinary Research in Health

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