Abstract：
Indole serves as a signaling molecule that could regulate different bacterial physiological processes, including antibiotic resistance through biofilm formation and drug efflux pump activity. In Escherichia coli, indole is produced through the tryptophan pathway, which involves three permeases (Mtr, AroP, and TnaB) that can transport the amino acid tryptophan. Although these permeases play distinct roles in the secretion of indole biosynthesis, their impact on multidrug resistance mediated by indole remaines unclear. This study was designed to investigate the connection between the tryptophan transport system and antibiotic resistance by constructing seven gene deletion mutants from E. coli MG1655 (wild type). Our result showed that deletion of the aroP or tnaB gene led to increased antibiotic resistance as evaluated by MICs for different antibiotics. Efflux activity test results revealed that the increased antibiotic resistance was related with the AcrAB-Tolc drug efflux pump in the mutants. The transcriptome analysis further demonstrated that decreased susceptibility to kanamycin and ampicillin in E. coli was accompanied by reduced accumulation of reactive oxygen species and decreased motility. These findings highlight the substantial influence of the tryptophan transport system on antibiotic resistance in E. coli, which is crucial for developing strategies against antibiotic resistance in bacterial infections.
摘要：
吲哚作为信号分子，可以调节不同的细菌生理过程，包括通过生物膜形成和药物外排泵活性的抗生素抗性。在大肠杆菌(E.大肠杆菌)，吲哚是通过色氨酸途径产生的，其中涉及三个permeases(Mtr，AroP,和TnaB），可以运输氨基酸色氨酸。尽管这些在吲哚生物合成的分泌中具有明显的作用，它们对吲哚介导的多药耐药的影响尚不清楚.本研究旨在通过构建7个来自大肠杆菌MG1655（野生型）的基因缺失突变体来研究色氨酸转运系统与抗生素抗性之间的联系。我们的结果表明，根据MIC对不同抗生素的评估，aroP或tnaB基因的缺失导致抗生素耐药性增加。外排活性测试结果表明，突变体中抗生素耐药性的增加与AcrAB-Tolc药物外排泵有关。转录组分析进一步证明,大肠杆菌中对卡那霉素和氨苄青霉素的敏感性降低伴随着活性氧(ROS)积累的降低和运动性的降低。这些发现强调了色氨酸转运系统对大肠杆菌抗生素耐药性的实质性影响，这对于制定针对细菌感染中抗生素耐药性的策略至关重要。
