A novel in-silico strategy for the combined inhibition of intestinal bacterial resistance and the transfer of resistant genes using new fluoroquinolones, antibiotic adjuvants, and phytochemicals
Qikun Pu , Zhonghe Wang , Tong Li , Qing Li , Meijin Du , Wenwen Wang , Yu Li
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引用次数: 0
Abstract
The antibiotic resistance and transfer of antibiotic resistance genes (ARGs) lead to severe environmental threats, and efficient regulatory measures to solve the above problems are urgently needed. Thus, a novel three-dimensional quantitative structure-activity relationship for S. aureus antibiotic resistance was constructed in this study. A fluoroquinolone (FQ) substitute (CIP-098) with decreased bacterial resistance by 15.19% and antibiotic adjuvant (2-phenylquinoline efflux pump inhibitor (2P-Q-EPI) substitute (Z-20)) that enhanced efflux pump inhibition by 1.96 times were designed. Mechanism analysis revealed that hydrogen bond donors and hydrogen bonding in FQ are essential groups and non-covalent interactions, which assist antibiotics in combating resistance mutations in S. aureus's DNA gyrase that transition from hydrophilic to hydrophobic residues. Z-20 was found to easily bind to key amino acid residues (Phe-16, Ile-19), thus reducing the antibiotic expulsion by the NorA efflux pump protein, which can inhibit antibiotic resistance in bacteria. The non-antibiotic factor regulatory scheme designed in this study significantly reduced (by 39.70%) the efflux of FQ by S. aureus and the risk of horizontal ARGs transfer. This study proposes a new strategy to mitigate FQ antibiotic resistance and ARGs transfer in gut microbiota, offering technical support for the green development of FQ antibiotics and 2P-Q-EPI.
Food BioscienceBiochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
6.40
自引率
5.80%
发文量
671
审稿时长
27 days
期刊介绍:
Food Bioscience is a peer-reviewed journal that aims to provide a forum for recent developments in the field of bio-related food research. The journal focuses on both fundamental and applied research worldwide, with special attention to ethnic and cultural aspects of food bioresearch.