title: Effect of serine protease KEX2 on Candida albicans virulence under halogenated methyl sulfones.
abstract: 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.
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Staniszewska
authors.affiliation: Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bondaryk
authors.affiliation: Laboratory of Physiology, The Witold Stefański Institute of Parasitology, Polish Academy of Science, Twarda 51/55, 00-818 Warsaw, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Kazek
authors.affiliation: Laboratory of Medical Entomology and Pest Control, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gliniewicz
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Liebermeisterstr.25, Tübingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Braunsdorf
authors.affiliation: Department of Dermatology, University Hospital Tübingen, Liebermeisterstr.25, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schaller
authors.affiliation: 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.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Mora-Montes
authors.affiliation: Warsaw University of Technology, Faculty of Chemistry, Institute of Biotechnology, Noakowskiego 3, 00-664 Warsaw, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Ochal
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D002177:Candidiasis / Q000382:microbiology; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000382:microbiology; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D005656:Fungal Proteins; D013450:Sulfones; C025910:dimethyl sulfone; D057057:Serine Proteases; D004121:Dimethyl Sulfoxide
keywords: C. albicans; adherence; host–pathogen interactions; pathogenesis; sulfones activity