title: Beyond ergosterol: linking pH to antifungal mechanisms.
abstract: Many antifungal drugs including the highly successful azoles target the fungal-specific sterol, ergosterol, yet the molecular identity of cellular pathways mediating antifungal activity remained obscure. A recent study on the requirement of ergosterol in vacuolar H+-ATPase (V-ATPase) function uncovered a critical role for ion homeostasis downstream of azole inhibition of ergosterol biosynthesis. Here we review the functional link between regulation of V-ATPase by fungal membrane lipid components and discuss contributions of V-ATPase function to pathogenicity. The importance of pH homeostasis in virulence highlights its potential as target in antifungal chemotherapy.
authors.affiliation: Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Zhang
authors.forename: Rajini
authors.initials: R
authors.lastname: Rao
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D001393:Azoles / Q000378:metabolism / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D004875:Ergosterol / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008563:Membrane Lipids; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D037521:Virulence Factors
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D008563:Membrane Lipids; D037521:Virulence Factors; D025262:Vacuolar Proton-Translocating ATPases; D004875:Ergosterol