Fungal sphingolipids: role in the regulation of virulence and potential as targets for future antifungal therapies.

Expert Review of Anti-infective Therapy
Caroline Mota Fernandes, Maurizio Del Poeta

Abstract

The antifungal therapy currently available includes three major classes of drugs: polyenes, azoles and echinocandins. However, the clinical use of these compounds faces several challenges: while polyenes are toxic to the host, antifungal resistance to azoles and echinocandins has been reported. Fungal sphingolipids (SL) play a pivotal role in growth, morphogenesis and virulence. In addition, fungi possess unique enzymes involved in SL synthesis, leading to the production of lipids which are absent or differ structurally from the mammalian counterparts. In this review, we address the enzymatic reactions involved in the SL synthesis and their relevance to the fungal pathogenesis, highlighting their potential as targets for novel drugs and the inhibitors described so far. The pharmacological inhibition of fungal serine palmitoyltransferase depends on the development of specific drugs, as myriocin also targets the mammalian enzyme. Inhibitors of ceramide synthase might constitute potent antifungals, by depleting the pool of complex SL and leading to the accumulation of the toxic intermediates. Acylhydrazones and aureobasidin A, which inhibit GlcCer and IPC synthesis, are not toxic to the host and effectively treat invasive mycoses,...Continue Reading

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Citations

Nov 4, 2020·FEBS Letters·Filipa C SantosRodrigo F M de Almeida
Mar 5, 2021·The Journal of Biological Chemistry·Velayoudame ParthibaneJairaj K Acharya
Apr 4, 2021·Bioorganic & Medicinal Chemistry Letters·Mostafa TeymuriMehdi Razzaghi-Abyaneh
Aug 20, 2021·Frontiers in Microbiology·Jian WangNan Yao

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