TY - JOUR
T1 - Induction of amphotericin B resistance in susceptible Candida auris by extracellular vesicles
AU - Chan, Walton
AU - Chow, Franklin Wang Ngai
AU - Tsang, Chi Ching
AU - Liu, Xueyan
AU - Yao, Weiming
AU - Chan, Tony Tat Yin
AU - Siu, Gilman Kit Hang
AU - Ho, Alex Yat Man
AU - Luk, Kristine Shik
AU - Lau, Susanna Kar Pui
AU - Woo, Patrick Chiu Yat
N1 - Funding Information:
This work was partly supported by the General Research Fund, Research Grants Council, University Grants Committee; as well as the framework of the Higher Education Sprout Project by the Ministry of Education (MOE-111-S-023-A) in Taiwan. We thank the Department of Pathology, HKU for the use of their nanoparticle tracking analysis machine and technical expertise; the Electron Microscope Unit, HKU for their technical support and assistance in sample preparation for TEM; and the Proteomics and Metabolomics Unit, HKU for their technical support and assistance in performing LC–MS.
Publisher Copyright:
© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - amphotericin B
KW - Candida auris
KW - drug resistance
KW - extracellular vesicles
KW - solid media EV purification
UR - http://www.scopus.com/inward/record.url?scp=85135026439&partnerID=8YFLogxK
U2 - 10.1080/22221751.2022.2098058
DO - 10.1080/22221751.2022.2098058
M3 - Journal article
C2 - 35786393
AN - SCOPUS:85135026439
SN - 2222-1751
VL - 11
SP - 1900
EP - 1909
JO - Emerging Microbes and Infections
JF - Emerging Microbes and Infections
IS - 1
ER -