2. Academic Validation
  3. Pantothenate kinase is an effective target for antifungal therapy

Pantothenate kinase is an effective target for antifungal therapy

  • Cell Chem Biol. 2025 May 15;32(5):710-721.e6. doi: 10.1016/j.chembiol.2025.04.007.
Jessica Regan 1,  Christian DeJarnette 2,  Parker Reitler 3,  Shalev Gihaz 4,  Ashish Srivastava 1,  Wenbo Ge 2,  Katie M Tucker 2,  Tracy L Peters 2,  Bernd Meibohm 1,  Choukri Ben Mamoun 4,  Jarrod R Fortwendel 2,  Kirk E Hevener 5,  Glen E Palmer 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, TN, USA.
  • 2 Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, TN, USA.
  • 3 Department of Molecular Immunology and Biochemistry, College of Graduate Health Sciences, University of Tennessee Health Sciences Center, Memphis, TN, USA.
  • 4 Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
  • 5 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, TN, USA. Electronic address: khevener@uthsc.edu.
  • 6 Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Sciences Center, Memphis, TN, USA. Electronic address: gpalmer5@uthsc.edu.
PMID: 40378822 DOI: 10.1016/j.chembiol.2025.04.007
Abstract

Pantothenate kinase (PANK) catalyzes the first step in the conversion of pantothenate to coenzyme A (CoA), an essential cofactor in all living organisms. The findings of this study demonstrate that PANK is essential for the viability and virulence of two of the most medically significant fungi-the pathogenic yeast Candida albicans, and the infectious mold Aspergillus fumigatus-within the mammalian host. Biochemical, biophysical as well as chemical-genetic approaches were applied to identify 3,4-methylenedioxy-β-nitrostyrene (MNS) as a broad-spectrum Antifungal that directly engages and inhibits PANK to block CoA production. Importantly, MNS is inactive against a mammalian PANK and demonstrates in vivo Antifungal efficacy a mouse model of disseminated C. albicans Infection. Thus, MNS has provided a valuable chemical probe to establish the validity of targeting PANK with small molecule inhibitors as a strategy to develop efficacious Antifungal therapeutics.

Keywords

Aspergillus; Cab1p; Candida; antifungal; coenzyme A; mycology; pantothenate kinase.

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