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坎地沙坦和多潘立酮抑制白色念珠菌毒力。

Impeding Virulence of Candida albicans by Candesartan and Domperidone.

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt.

Department of Microbiology and Immunology, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, Cairo, 11829, Egypt.

出版信息

Curr Microbiol. 2021 Nov;78(11):3957-3967. doi: 10.1007/s00284-021-02663-x. Epub 2021 Sep 22.

Abstract

Candida albicans is the most common human fungal pathogen that has developed extensive virulence factors which allows successful colonization and infection of the host. Anti-virulence agents can alleviate the pathogenesis of fungi and help the immune system to eradicate them easily. This study aimed to explore the anti-virulence effect of domperidone and candesartan against C. albicans standard strain. Sub-inhibitory concentrations (1/4 and 1/8 of minimum inhibitory concentration) of domperidone and candesartan significantly inhibited the virulence factors hemolysin, lipase, protease, phospholipase, and bioflim formation. It was found that candesartan inhibited biofilm formation by 60.48-67.91%, hemolysin activity (61.21-74.14%), phospholipase activity (40-49.67%), lipase activity (58.97-73%), and protease activity (52.63%), while domperidone was found to inhibit biofilm formation by 70.54-77.49%, hemolysin activity (64.84-69.84%), phospholipase activity (49.67-60%), lipase activity (50-54.87%), and protease activity (52.63-57.9%). Quantitative real time-PCR confirmed the anti-virulence activity of domperidone and candesartan as both drugs significantly reduce the expression of the virulence genes SAP2, SAP6, PLB1, PLB2, LIP4, LIP5. In conclusion, domperidone and candesartan could serve as anti-virulence agents for treatment of C. albicans infections.

摘要

白色念珠菌是最常见的人类真菌病原体,它已经发展出广泛的毒力因子,使其能够成功定植和感染宿主。抗毒力药物可以减轻真菌的发病机制,并帮助免疫系统更容易地消灭它们。本研究旨在探索多潘立酮和坎地沙坦对白色念珠菌标准株的抗毒力作用。多潘立酮和坎地沙坦的亚抑菌浓度(最低抑菌浓度的 1/4 和 1/8)显著抑制了溶血素、脂肪酶、蛋白酶、磷脂酶和生物膜形成等毒力因子。研究发现,坎地沙坦抑制生物膜形成的能力为 60.48-67.91%,溶血素活性为 61.21-74.14%,磷脂酶活性为 40-49.67%,脂肪酶活性为 58.97-73%,蛋白酶活性为 52.63%,而多潘立酮则抑制生物膜形成的能力为 70.54-77.49%,溶血素活性为 64.84-69.84%,磷脂酶活性为 49.67-60%,脂肪酶活性为 50-54.87%,蛋白酶活性为 52.63-57.9%。实时定量 PCR 证实了多潘立酮和坎地沙坦的抗毒力活性,这两种药物均显著降低了毒力基因 SAP2、SAP6、PLB1、PLB2、LIP4、LIP5 的表达。综上所述,多潘立酮和坎地沙坦可以作为治疗白色念珠菌感染的抗毒力药物。

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