丝氨酸蛋白酶KEX2在卤代甲基砜作用下对白色念珠菌毒力的影响
Effect of serine protease KEX2 on Candida albicans virulence under halogenated methyl sulfones.
作者信息
Staniszewska Monika, Bondaryk Małgorzata, Kazek Michalina, Gliniewicz Aleksandra, Braunsdorf Christina, Schaller Martin, Mora-Montes Hector M, Ochal Zbigniew
机构信息
Independent Laboratory of Streptomyces and Fungi Imperfecti, National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warsaw, Poland.
Laboratory of Physiology, The Witold Stefański Institute of Parasitology, Polish Academy of Science, Twarda 51/55, 00-818 Warsaw, Poland.
出版信息
Future Microbiol. 2017 Mar;12:285-306. doi: 10.2217/fmb-2016-0141. Epub 2017 Feb 24.
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.
目的
评估KEX2突变对白色念珠菌毒力及对卤代甲基砜耐药性的影响。
材料与方法
使用流式细胞术和显微镜研究砜类药物的作用机制。采用定量实时聚合酶链反应评估KEX2和SAP5的表达。分别设计2,3-双(2-甲氧基-4-硝基-5-磺基苯基)-2H-四唑-5-羧基苯胺和乳酸脱氢酶检测法，以研究经砜类药物处理的念珠菌的代谢及其对组织的细胞毒性。通过酶联免疫吸附测定法检测炎症反应。
结果
观察到砜类药物作用下溶酶体通透性增加和剂量依赖性程序性细胞死亡。KEX2的诱导依赖于卤代甲基磺酰基，其影响细胞壁生物合成和黏附。
结论
砜类药物处理降低了蜡螟幼虫体内白色念珠菌的致病性。由于其安全性和抗生物膜活性，砜类药物可作为抗真菌治疗的替代药物。
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