Evolution of multi-drug resistance in candida auris in vitro and in patients undergoing antifungal treatment

The National Institute of Allergy and Infectious Diseases awarded the University of Maryland, Baltimore $233,250 in project grant funding (R21AI199182) on September 2, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855).

The award funds research to characterize the evolution of multidrug resistance in Candida auris, a newly emerged fungal pathogen associated with invasive candidiasis worldwide and mortality rates approaching 68 percent. The recipient will prospectively recover clinical isolates of C. auris that have acquired multidrug resistance during patient antifungal treatment and comprehensively evaluate them for phenotypic, genomic, and transcriptional alterations associated with drug resistance, cell function, and fitness. The research aims to provide mechanistic insights into how C. auris adapts to therapeutic stress and to identify potential targets or adjunctive therapies to overcome antifungal drug resistance.

Work is performed at the Baltimore, Maryland campus location. The award period of performance runs through August 31, 2028.

Abstract

Candida auris is a newly emerged human fungal pathogen associated with an exponential rise in invasive candidiasis worldwide with mortality rates approaching 68%. Most concerning is the unique ability of C. Auris to develop multidrug resistance to all main classes of antifungals. In this proposal, we hypothesize that clinical antifungal therapy induces development of drug resistance in C. Auris as well phenotypic and transcriptional alterations impacting cell function, fitness and pathogenic potential. To that end, prospectively recovered isolates which have acquired multi-drug resistance in patients during therapy will be comprehensively evaluated for phenotypic, genomic, and transcriptional alterations associated with drug resistance, cell function and fitness. When completed, the proposed aims will provide mechanistic insights into how C. Auris evolves and adapts to stresses to ensure survival in the host. Importantly, the findings generated will aid in the development of potential adjunctive/combinatorial therapies to overcome drug resistance or identify new targets to enhance effectiveness of antifungals.