Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris

Jeffrey M. Rybak, Laura A. Doorley, Andrew T. Nishimoto, Katherine S. Barker, Glen Palmer, Phillip Rogers

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Candida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida albicans CDR1 and MDR1 among three triazole-resistant clinical isolates as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete C. auris CDR1 and MDR1 in both a triazole-resistant clinical isolate and a susceptible reference strain and observed that MICs for all clinically available triazoles decreased as much as 128-fold in the CDR1 deletion strains. The findings of this work reveal for the first time that C. auris CDR1 and MDR1 are more highly expressed among triazole-resistant clinical isolates of C. auris and that the overexpression of CDR1 is a significant contributor to clinical triazole resistance.

Original languageEnglish (US)
Article numbere00057-19
JournalAntimicrobial Agents and Chemotherapy
DOIs
StatePublished - Apr 1 2019

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Triazoles
Candida
Candida albicans
Genome
Delivery of Health Care
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris. / Rybak, Jeffrey M.; Doorley, Laura A.; Nishimoto, Andrew T.; Barker, Katherine S.; Palmer, Glen; Rogers, Phillip.

In: Antimicrobial Agents and Chemotherapy, 01.04.2019.

Research output: Contribution to journalArticle

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