Sterol Biosynthesis Is Required for Heat Resistance but Not Extracellular Survival in

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Leishmania parasites are transmitted through the bite of sandflies causing a spectrum of serious diseases in humans. Current drugs are inadequate and no safe vaccine is available. These parasites produce different types of sterols from humans, making the sterol synthesis pathway a valuable target of selective inhibitors. However, functions of sterols and sterol synthesis in protozoa are poorly understood, which hinders the development of new and improved treatments. In this study, we investigated the role of sterol C14α-demethylase, a key enzyme in sterol metabolism and the primary target of azole drugs. Loss of sterol C14α-demethylase completely altered the sterol composition in Leishmania, leading to increased membrane fluidity, failure to maintain lipid rafts, and hypersensitivity to heat stress. Despite these defects, null mutants of sterol C14α-demethylase were viable during the promastigote stage (found in sandflies) and could still cause disease in mice (although at a reduced capacity). Our findings provide direct evidence to support the role of specific sterols in membrane stability and stress response. The new knowledge may also help the development of new treatments or improve the efficacy of current drugs against pathogenic protozoa.

Vyšlo v časopise: Sterol Biosynthesis Is Required for Heat Resistance but Not Extracellular Survival in. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004427
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004427

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