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甲氧基取代的羟基查耳酮通过抑制 ompA 基因表达减少鲍曼不动杆菌生物膜的产生、黏附和表面迁移。

Methoxy-Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of Acinetobacter baumannii by Inhibiting ompA Gene Expression.

机构信息

Department of Microbiology and Immunology, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11221, Belgrade, Serbia.

Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Vojvode Stepe 444/a, 11010, Belgrade, Serbia.

出版信息

Chem Biodivers. 2021 Jan;18(1):e2000786. doi: 10.1002/cbdv.202000786. Epub 2020 Dec 7.

Abstract

An increasing lack of available therapeutic options against Acinetobacter baumannii urged researchers to seek alternative ways to fight this extremely resistant nosocomial pathogen. Targeting its virulence appears to be a promising strategy, as it offers considerably reduced selection of resistant mutants. In this study, we tested antibiofilm potential of four synthetic chalcone derivatives against A. baumannii. Compound that showed the greatest activity was selected for further evaluation of its antivirulence properties. Real-time PCR was used to evaluate mRNA expression of biofilm-associated virulence factor genes (ompA, bap, abaI) in treated A. baumannii strains. Also, we examined virulence properties related to the expression of these genes, such as fibronectin- and collagen-mediated adhesion, surface motility, and quorum-sensing activity. The results revealed that the expression of all tested genes is downregulated together with the reduction of adhesion and motility. The conclusion is that 2'-hydroxy-2-methoxychalcone exhibits antivirulence activity against A. baumannii by inhibiting the expression of ompA and bap genes, which is reflected in reduced biofilm formation, adhesion, and surface motility.

摘要

针对鲍曼不动杆菌可用的治疗选择越来越少,这促使研究人员寻求对抗这种极具耐药性的医院获得性病原体的替代方法。针对其毒力似乎是一种很有前途的策略,因为它可以大大减少耐药突变体的选择。在这项研究中,我们测试了四种合成查尔酮衍生物对鲍曼不动杆菌的抗生物膜潜力。表现出最大活性的化合物被选中,以进一步评估其抗毒力特性。实时 PCR 用于评估处理过的鲍曼不动杆菌菌株中与生物膜相关的毒力因子基因 (ompA、bap、abaI) 的 mRNA 表达。此外,我们还研究了与这些基因表达相关的毒力特性,如纤维连接蛋白和胶原蛋白介导的粘附、表面运动性和群体感应活性。结果表明,所有测试基因的表达均下调,同时粘附和运动性降低。结论是,2'-羟基-2-甲氧基查尔酮通过抑制 ompA 和 bap 基因的表达表现出抗鲍曼不动杆菌的抗病毒活性,这反映在生物膜形成、粘附和表面运动性降低上。

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