Effect of serine protease KEX2 on Candida albicans virulence under halogenated methyl sulfones

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-...

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Bibliographic Details
Published in:Future microbiology 2017-03, Vol.12 (4), p.285-306
Main Authors: Staniszewska, Monika, Bondaryk, Małgorzata, Kazek, Michalina, Gliniewicz, Aleksandra, Braunsdorf, Christina, Schaller, Martin, Mora-Montes, Hector M, Ochal, Zbigniew
Format: Article
Language:English
Subjects:
Animals
Antifungal Agents - pharmacology
Apoptosis
Biofilms - drug effects
Biosynthesis
Candida
Candida albicans
Candida albicans - drug effects
Candida albicans - enzymology
Candida albicans - genetics
Candida albicans - pathogenicity
Candidiasis - microbiology
Cell death
Cell Wall - drug effects
Cell Wall - metabolism
Cell walls
Cytotoxicity
Dimethyl Sulfoxide - pharmacology
Enzyme-linked immunosorbent assay
Experiments
Flow cytometry
Fungal Proteins - genetics
Fungal Proteins - metabolism
Galleria mellonella
Humans
Infections
Inflammation
L-Lactate dehydrogenase
Lactic acid
Metabolism
Microbial Sensitivity Tests
Moths - microbiology
Pathogenicity
Pathogens
Serine
Serine Proteases - genetics
Serine Proteases - metabolism
Serine proteinase
Sulfones - pharmacology
Virulence
Virulence - drug effects
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Summary: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.
ISSN:1746-0913
1746-0921
DOI:10.2217/fmb-2016-0141