Research News
Researchers Reveal Fungicide-tolerant Persister Formation During Cryptococcal Pulmonary Infection
Editor: LIU Jia | Jan 19, 2024
Print

Microbial persisters, a subpopulation of genetically susceptible cells that are normally dormant and tolerant to antimicrobial agents, are considered to be an important contributor to recurrent infections and drug treatment failure. The formation of fungicide-tolerant fungal persisters has not been directly observed in vivo during fungal disease. 

In a study published in Cell Host & Microbe, Dr. WANG Linqi’s group and Dr. Yu V Fu’s group from the Institute of Microbiology of the Chinese Academy of Sciences have demonstrated that the human fungal pathogen Cryptococcus neoformans (C. neoformans) can form persisters during lung infection that are highly tolerant to amphotericin B (AmB), the only approved fungicide for the treatment of cryptococcal infections. 

A major bottleneck in the study of fungicide persistence is the lack of cell tracking methods to sort and assess the highly heterogeneous fungal cell subpopulations in vivo

By exploring stationary phase indicator molecules and developing single-cell tracking strategies, the researchers showed that in the mouse lung, AmB persisters are highly enriched in cryptococcal cells that abundantly produce these molecules.

AmB persistence in C. neoformans involves two parallel mechanisms: inhibition of energy metabolism and activation of antioxidant systems, in which a cryptococcal stationary phase antioxidant, ergothioneine, plays a central role. Remarkably, ergothioneine-mediated AmB persistence is conserved in different fungi.
Furthermore, the researchers showed that screening of a library of Food and Drug Administration (FDA)-approved drugs revealed a specific efficacy of the antidepressant sertraline against cryptococcal persisters.
The study was done in collaboration with Tongji University, Southwest University, and Georgetown University.
Contact

WANG Linqi

Institute of Microbiology

E-mail:

Related Articles