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

被引:14
|
作者
Staniszewska, Monika [1 ]
Bondaryk, Malgorzata [1 ]
Kazek, Michalina [2 ]
Gliniewicz, Aleksandra [3 ]
Braunsdorf, Christina [4 ]
Schaller, Martin [4 ]
Mora-Montes, Hector M. [5 ]
Ochal, Zbigniew [6 ]
机构
[1] Natl Inst Hyg, Natl Inst Publ Hlth, Independent Lab Streptomyces & Fungi Imperfecti, Chocimska 24, PL-00791 Warsaw, Poland
[2] Polish Acad Sci, Witold Stefanski Inst Parasitol, Lab Physiol, Twarda 51-55, PL-00818 Warsaw, Poland
[3] Natl Inst Hyg, Lab Med Entomol & Pest Control, Natl Inst Publ Hlth, Chocimska 24, PL-00791 Warsaw, Poland
[4] Univ Hosp Tubingen, Dept Dermatol, Liebermeisterstr 25, Tubingen, Germany
[5] Univ Guanajuato, Dept Biol, Div Ciencias Nat & Exactas, Campus Guanajuato,Noria Alta S-N,Col Noria Alta, Guanajuato 36050, Gto, Mexico
[6] Warsaw Univ Technol, Inst Biotechnol, Fac Chem, Noakowskiego 3, PL-00664 Warsaw, Poland
关键词
adherence; C; albicans; host-pathogen; interactions; pathogenesis; sulfones activity; IN-VITRO; AMPHOTERICIN-B; CELL-WALL; APOPTOSIS; GROWTH; CASPOFUNGIN; PEPTIDE; GENE; EXPRESSION; MECHANISM;
D O I
10.2217/fmb-2016-0141
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:285 / 306
页数:22
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