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The effect of KEX2 mutations on C. albicans virulence and resistance to halogenated methyl sulfones was assessed. The mechanism of action of sulfones was studied using flow cytometry and microscopy. Expression of KEX2 and SAP5 was assessed using quantitative Real-Time-PCR. 2,3-Bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide and lactate dehydrogenase assays were elaborated to study, respectively, metabolism of Candida treated with sulfones and their cytotoxicity against tissues. Inflammatory response was detected by ELISA. Lysosome permeabilization and dose-dependent programmed cell death under sulfones were noted. KEX2 induction depended on halogenomethylsulfonyl groups, which affected cell wall biosynthesis and adhesion. Sulfones treatment reduced Candida pathogenicity in Galleria mellonella. Sulfones are an alternative for antifungal therapies due to their safety profile and antibiofilm activity.

Citation

Monika Staniszewska, Małgorzata Bondaryk, Michalina Kazek, Aleksandra Gliniewicz, Christina Braunsdorf, Martin Schaller, Hector M Mora-Montes, Zbigniew Ochal. Effect of serine protease KEX2 on Candida albicans virulence under halogenated methyl sulfones. Future microbiology. 2017 Mar;12:285-306

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PMID: 28287299

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