Induction of amphotericin B resistance in susceptible Candida auris by extracellular vesicles

Walton Chan, Franklin Wang Ngai Chow, Chi Ching Tsang, Xueyan Liu, Weiming Yao, Tony Tat Yin Chan, Gilman Kit Hang Siu, Alex Yat Man Ho, Kristine Shik Luk, Susanna Kar Pui Lau, Patrick Chiu Yat Woo

Research output: Journal article publicationJournal articleAcademic researchpeer-review

10 Citations (Scopus)

Abstract

Drug resistance derived from extracellular vesicles (EVs) is an increasingly important research area but has seldom been described regarding fungal pathogens. Here, we characterized EVs derived from a triazole-resistant but amphotericin B-susceptible strain of Candida auris. Nano- to microgram concentrations of C. auris EVs prepared from both broth and solid agar cultures could robustly increase the yeast’s survival against both pure and clinical amphotericin B formulations in a dose-dependent manner, resulting in up to 16-fold changes of minimum inhibitory concentration. Meanwhile, this effect was not observed upon addition of these EVs to C. albicans, nor upon addition of C. albicans EVs to C. auris. No change in susceptibilities was observed upon EV treatment for fluconazole, voriconazole, micafungin, and flucytosine. Mass spectrometry indicated the presence of immunogenic-/drug resistance-implicated proteins in C. auris EVs, including alcohol dehydrogenase 1 as well as C. albicans Mp65-like and Xog1-like proteins in high quantities. Based on these observations, we propose a potential species-specific role for EVs in amphotericin B resistance in C. auris. These observations may provide critical insights into treatment of multidrug-resistant C. auris.

Original languageEnglish
Pages (from-to)1900-1909
Number of pages10
JournalEmerging Microbes and Infections
Volume11
Issue number1
DOIs
Publication statusPublished - Dec 2022

Keywords

  • amphotericin B
  • Candida auris
  • drug resistance
  • extracellular vesicles
  • solid media EV purification

ASJC Scopus subject areas

  • Epidemiology
  • Parasitology
  • Microbiology
  • Immunology
  • Drug Discovery
  • Infectious Diseases
  • Virology

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