Efflux pump inhibition disrupts biofilms and enhances azole susceptibility in Candidozyma auris

Candidozyma auris (formerly Candida auris) is a global emerging fungal pathogen of significant global clinical and epidemiological concern. It is frequently associated with hospital outbreaks, largely due to its multidrug resistance, ability to persist on medical devices, and high potential for nosocomial transmission. This study investigated efflux pump inhibition as a potential strategy for controlling C. auris. The efflux pump inhibitor promethazine (PMZ) was evaluated against planktonic cells and mature biofilms of 15 clinical isolates. PMZ completely inhibited the planktonic growth of both azole-susceptible and azole-resistant C. auris strains at concentrations ranging from 32 to 64 μg/mL. Synergistic interactions between PMZ and either echinocandins or azoles were observed, resulting in effective inhibition of nearly all tested strains during planktonic phase growth. Additionally, PMZ at 4× MIC significantly disrupted mature biofilms of both azole-susceptible and azole-resistant strains. Mature biofilms were also susceptible to combinations of antifungals and PMZ. These findings indicate that efflux pump inhibition represents a promising therapeutic strategy for controlling infections caused by C. auris. PMZ may be considered a promising structural framework for the development of novel antifungal agents.