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

Author:

Staniszewska Monika1,Bondaryk Małgorzata1,Kazek Michalina2,Gliniewicz Aleksandra3,Braunsdorf Christina4,Schaller Martin4,Mora-Montes Hector M5,Ochal Zbigniew6

Affiliation:

1. Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health–National Institute of Hygiene, Chocimska 24, 00–791 Warsaw, Poland

2. Laboratory of Physiology, The Witold Stefański Institute of Parasitology, Polish Academy of Science, Twarda 51/55, 00–818 Warsaw, Poland

3. Laboratory of Medical Entomology and Pest Control, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland

4. Department of Dermatology, University Hospital Tübingen, Liebermeisterstr.25, Tübingen, Germany

5. Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato, Noria Alta s/n, col. Noria Alta, C.P. 36050, Guanajuato, Gto., México

6. Warsaw University of Technology, Faculty of Chemistry, Institute of Biotechnology, Noakowskiego 3, 00-664 Warsaw, Poland

Abstract

Aim: The effect of KEX2 mutations on C. albicans virulence and resistance to halogenated methyl sulfones was assessed. Materials & methods: 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. Results: 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. Conclusion: Sulfones treatment reduced Candida pathogenicity in Galleria mellonella. Sulfones are an alternative for antifungal therapies due to their safety profile and antibiofilm activity.

Publisher

Future Medicine Ltd

Subject

Microbiology (medical),Microbiology

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