Identification and Elimination of Antifungal Tolerance in Candida auris

Author:

Rasouli Koohi Samira1ORCID,Shankarnarayan Shamanth A.1ORCID,Galon Clare Maristela1,Charlebois Daniel A.12ORCID

Affiliation:

1. Department of Physics, University of Alberta, Edmonton, AB T6G 2R3, Canada

2. Department of Biological Sciences, University of Alberta, Edmonton, AB T6G 2E9, Canada

Abstract

Antimicrobial resistance is a global health crisis to which pathogenic fungi make a substantial contribution. The human fungal pathogen C. auris is of particular concern due to its rapid spread across the world and its evolution of multidrug resistance. Fluconazole failure in C. auris has been recently attributed to antifungal “tolerance”. Tolerance is a phenomenon whereby a slow-growing subpopulation of tolerant cells, which are genetically identical to susceptible cells, emerges during drug treatment. We use microbroth dilution and disk diffusion assays, together with image analysis, to investigate antifungal tolerance in C. auris to all three classes of antifungal drugs used to treat invasive candidiasis. We find that (1) C. auris is tolerant to several common fungistatic and fungicidal drugs, which in some cases can be detected after 24 h, as well as after 48 h, of antifungal drug exposure; (2) the tolerant phenotype reverts to the susceptible phenotype in C. auris; and (3) combining azole, polyene, and echinocandin antifungal drugs with the adjuvant chloroquine in some cases reduces or eliminates tolerance and resistance in patient-derived C. auris isolates. These results suggest that tolerance contributes to treatment failure in C. auris infections for a broad range of antifungal drugs, and that antifungal adjuvants may improve treatment outcomes for patients infected with antifungal-tolerant or antifungal-resistant fungal pathogens.

Funder

Government of Canada’s New Frontiers in Research Fund—Exploration

Canadian Foundation for Innovation’s John R. Evans Leaders Fund

Government of Alberta’s Research Capacity Program

Audrey and Randy Lomnes Early Career Endowment Award

DOST-SEI-UAlberta S&T Graduate Scholarship Program

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Reference62 articles.

1. The Global Problem of Antifungal Resistance: Prevalence, Mechanisms, and Management;Perlin;Lancet Infect. Dis.,2017

2. The Importance of Antimicrobial Resistance in Medical Mycology;Gow;Nat. Commun.,2022

3. Nosocomial Fungal Infections: Epidemiology, Infection Control, and Prevention;Alangaden;Infect. Dis. Clin. North Am.,2011

4. The Epidemiology and Outcomes of Invasive Candida Infections among Organ Transplant Recipients in the United States: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET);Andes;Transpl. Infect. Dis.,2016

5. O’Neill, J. (2022, November 10). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations: The Review on Antimicrobial Resistanc. Available online: https://Amr-Review.Org.

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3