Meropenem in combination with baicalein exhibits synergism against extensively drug resistant and pan-drug-resistant Acinetobacter baumannii clinical isolates in vitro.

IF 2.7 4区 医学 Q3 IMMUNOLOGY
Mümtaz Güran, Kadir Çakıral, Kerem Teralı, Tülay Kandemir, Gizem Şanlıtürk, Melda Meral Öcal, Toğrul Nagiyev, Fatih Köksal
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Abstract

Several studies have demonstrated that the effectiveness of carbapenems against drug-resistant Acinetobacter baumannii infections has been decreasing. Combination therapy with two or more drugs is currently under investigation to overcome the emerging resistance against carbapenems. In this study, we tested the possible synergistic interactions of a potent antibacterial flavonoid, baicalein, with meropenem to illustrate this duo's antibacterial and antibiofilm effects on 15 extensively drug resistant or pan-drug-resistant (XDR/PDR) A. baumannii clinical isolates in vitro. Isolates included in the study were identified with MALDI-TOF MS, and antibiotic resistance patterns were studied according to EUCAST protocols. Carbapenem resistance was confirmed with the modified Hodge test, and resistance genes were also analyzed with genotypical methods. Then, checkerboard and time-kill assays were performed to analyze antibacterial synergism. Additionally, a biofilm inhibition assay was performed for screening the antibiofilm activity. To provide structural and mechanistic insights into baicalein action, protein-ligand docking, and interaction profiling calculations were conducted. Our study shed light on the remarkable potential of the baicalein-meropenem combination, since either synergistic or additive antibacterial activity was observed against every XDR/PDR A. baumannii strain in question. Furthermore, the baicalein-meropenem combination displayed significantly better antibiofilm activity in contrast to standalone use. In silico studies predicted that these positive effects arose from inhibition by baicalein of A. baumannii beta-lactamases and/or penicillin-binding proteins. Overall, our findings highlight the prospective potential benefits of baicalein in combination with meropenem for the treatment of carbapenem-resistant A. baumannii infections.

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美罗培南联合黄芩素对广泛耐药和泛耐药鲍曼不动杆菌临床分离株有协同作用。
一些研究表明,碳青霉烯类药物对耐药鲍曼不动杆菌感染的有效性一直在下降。目前正在研究两种或两种以上药物的联合治疗,以克服对碳青霉烯类新出现的耐药性。在这项研究中,我们测试了一种有效的抗菌类黄酮黄芩素与美罗培南可能的协同相互作用,以说明这对组合对15种广泛耐药或泛耐药(XDR/PDR)鲍曼不动杆菌临床分离株的体外抗菌和抗生物膜作用。采用MALDI-TOF MS对纳入研究的分离株进行鉴定,并根据EUCAST协议研究抗生素耐药模式。采用改良的Hodge试验证实对碳青霉烯类耐药,并采用基因型分析耐药基因。然后采用棋盘法和时效法分析其抗菌增效作用。此外,进行了生物膜抑制试验以筛选抗生物膜活性。为了提供黄芩素作用的结构和机制见解,进行了蛋白质配体对接和相互作用分析计算。我们的研究揭示了黄芩素-美罗培南组合的显著潜力,因为无论是协同还是加性抗菌活性都被观察到对每一种XDR/PDR鲍曼尼杆菌菌株的抑菌活性。此外,黄芩素-美罗培南联合使用比单独使用表现出更好的抗菌活性。计算机研究预测,这些积极作用是由黄芩素抑制鲍曼不动杆菌β -内酰胺酶和/或青霉素结合蛋白引起的。总的来说,我们的研究结果强调了黄芩苷联合美罗培南治疗耐碳青霉烯鲍曼杆菌感染的潜在益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pathogens and disease
Pathogens and disease IMMUNOLOGY-INFECTIOUS DISEASES
CiteScore
7.40
自引率
3.00%
发文量
44
期刊介绍: Pathogens and Disease publishes outstanding primary research on hypothesis- and discovery-driven studies on pathogens, host-pathogen interactions, host response to infection and their molecular and cellular correlates. It covers all pathogens – eukaryotes, prokaryotes, and viruses – and includes zoonotic pathogens and experimental translational applications.
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