Monika Staniszewska1, Małgorzata Bondaryk1, Michalina Kazek2, Aleksandra Gliniewicz3, Christina Braunsdorf4, Martin Schaller4, Hector M Mora-Montes5, Zbigniew Ochal6. 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.
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.
Entities:
Keywords:
C. albicans; adherence; host–pathogen interactions; pathogenesis; sulfones activity