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Discovery and mechanism of a highly selective, antifungal acetyl-CoA synthetase inhibitor

Acetyl-CoA synthetases have been proposed as targets for development of new antimicrobial drugs. Here, Jezewski et al. identify isoxazole-based compounds with activity against the pathogenic fungus Cryptococcus neoformans, and describe their mechanism of action as inhibitors of fungal acetyl-CoA synthetases.

Andrew J. Jezewski
Katy M. Alden
Damian J. Krysan
ResearchOpen Access14 Oct 2025
Nature Communications

Volume: 16, P: 1-17
Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Here, Ristow et al show that the environmental fungus Cryptococcus adapts to the higher carbon dioxide levels present in human tissue through activation of the Target-of-Rapamycin stress response pathway leading to reorganization of its outer membrane lipids and host adaptation.

Laura C. Ristow
Andrew J. Jezewski
Damian J. Krysan
ResearchOpen Access18 Oct 2023
Nature Communications

Volume: 14, P: 1-15
Author Correction: Drug resistance and tolerance in fungi

Judith Berman
Damian J. Krysan
Amendments and Corrections29 Jun 2020
Nature Reviews Microbiology

Volume: 18, P: 539
Discovery of CO₂ tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans

Quantitative trait loci mapping reveals that tolerance to host CO₂ is critical for virulence of the human fungal pathogen Cryptococcus neoformans.

Benjamin J. Chadwick
Laura C. Ristow
Xiaorong Lin
Research04 Sept 2024
Nature Microbiology

Volume: 9, P: 2684-2695
Drug resistance and tolerance in fungi

In this Review, Berman and Krysan define and distinguish resistance and tolerance, and discuss the current understanding of the molecular, genetic and physiological mechanisms that contribute to those phenomena. Distinguishing tolerance from resistance might provide important insights into the reasons for treatment failure in some settings.

Judith Berman
Damian J. Krysan
Reviews11 Feb 2020
Nature Reviews Microbiology

Volume: 18, P: 319-331
Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus

The chaperone Hsp90 is a potential target for the development of drugs against fungal pathogens. Here the authors determine the structure of the Hsp90 nucleotide-binding domain from Candida albicans, which they use to design an inhibitor and demonstrate its selectivity for the fungal enzyme, both biochemically and in cells.

Luke Whitesell
Nicole Robbins
Leah E. Cowen
ResearchOpen Access24 Jan 2019
Nature Communications

Volume: 10, P: 1-17
The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

Cas5 is a transcriptional regulator of responses to cell wall stress in the fungal pathogen Candida albicans. Here, Xie et al. show that Cas5 also modulates cell cycle dynamics and responses to antifungal drugs.

Jinglin L. Xie
Longguang Qin
Leah E. Cowen
ResearchOpen Access11 Sept 2017
Nature Communications

Volume: 8, P: 1-18
A high-throughput assay of yeast cell lysis for drug discovery and genetic analysis

Louis DiDone
Thomas Scrimale
Damian J Krysan
Protocols27 May 2010
Nature Protocols

Volume: 5, P: 1107-1114

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Discovery and mechanism of a highly selective, antifungal acetyl-CoA synthetase inhibitor

Cryptococcus neoformans adapts to the host environment through TOR-mediated remodeling of phospholipid asymmetry

Author Correction: Drug resistance and tolerance in fungi

Discovery of CO₂ tolerance genes associated with virulence in the fungal pathogen Cryptococcus neoformans

Drug resistance and tolerance in fungi

Structural basis for species-selective targeting of Hsp90 in a pathogenic fungus

The Candida albicans transcription factor Cas5 couples stress responses, drug resistance and cell cycle regulation

A high-throughput assay of yeast cell lysis for drug discovery and genetic analysis

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