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Methoxy‐Substituted Hydroxychalcone Reduces Biofilm Production, Adhesion and Surface Motility of Acinetobacter baumannii by Inhibiting ompA Gene Expression
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2020-12-07 , DOI: 10.1002/cbdv.202000786
Dušan Ušjak 1 , Miroslav Dinić 2 , Katarina Novović 2 , Branka Ivković 3 , Nenad Filipović 4 , Magdalena Stevanović 4 , Marina T Milenković 1
Affiliation  

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.

中文翻译:

甲氧基取代的羟基查尔酮通过抑制 ompA 基因表达减少鲍曼不动杆菌的生物膜产生、粘附和表面运动

越来越缺乏针对鲍曼不动杆菌的可用治疗选择,这促使研究人员寻求替代方法来对抗这种极其耐药的医院病原体。针对其毒力似乎是一个很有前途的策略,因为它大大减少了抗性突变体的选择。在这项研究中,我们测试了四种合成查耳酮衍生物对鲍曼不动杆菌的抗生物膜潜力。选择显示最大活性的化合物以进一步评估其抗毒力特性。实时 PCR 用于评估经处理的鲍曼不动杆菌菌株中生物膜相关毒力因子基因(ompA、bap、abaI)的 mRNA 表达。此外,我们检查了与这些基因表达相关的毒力特性,例如纤连蛋白和胶原介导的粘附、表面运动和群体感应活动。结果表明,所有测试基因的表达都被下调,同时粘附和运动的减少。结论是,2'-羟基-2-甲氧基查尔酮通过抑制 ompA 和 bap 基因的表达对鲍曼不动杆菌表现出抗毒活性,这反映在生物膜形成、粘附和表面运动减少上。
更新日期:2020-12-07
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