Agrobacterium tumefaciens AcrR is the transcriptional repressor of the acrABR operon. The AcrAB efflux pump confers resistance to various toxic compounds, including antibiotics [ciprofloxacin (CIP), nalidixic acid (NAL), novobiocin (NOV) and tetracycline (TET)], a detergent [sodium dodecyl sulfate (SDS)] and a biocide [triclosan (TRI)]. The sequence to which AcrR specifically binds in the acrA promoter region was determined by EMSA and DNase I footprinting. The AcrR-DNA interaction was abolished by adding NAL, SDS and TRI. Quantitative real time-PCR analysis showed that induction of the acrA transcript occurred when wild-type cells were exposed to NAL, SDS and TRI. Indole is a signaling molecule that increases the antibiotic resistance of bacteria, at least in part, through activation of efflux pumps. Expression of the A. tumefaciens acrA transcript was also inducible by indole in a dose-dependent manner. Indole induced protection against CIP, NAL and SDS but enhanced susceptibility to NOV and TRI. Additionally, the TET resistance of A. tumefaciens was not apparently modulated by indole. A. tumefaciens AcrAB played a dominant role and was required for tolerance to high levels of the toxic compounds. Understanding the regulation of multidrug efflux pumps and bacterial adaptive responses to intracellular and extracellular signaling molecules for antibiotic resistance is essential. This information will be useful for the rational design of effective treatments for bacterial infection to overcome possible multidrug-resistant pathogens.

根癌农杆菌AcrR是acrABR操纵子的转录阻遏物。AcrAB外排泵可抵抗多种有毒化合物，包括抗生素[环丙沙星（CIP），萘啶酸（NAL），新霉素（NOV）和四环素（TET）]，清洁剂[十二烷基硫酸钠（SDS）]和杀菌剂[三氯生（TRI）]。AcrR在acrA启动子区域中特异性结合的序列由EMSA和DNase I足迹确定。通过添加NAL，SDS和TRI消除了AcrR-DNA的相互作用。实时荧光定量PCR分析表明acrA的诱导当野生型细胞暴露于NAL，SDS和TRI时，转录发生。吲哚是一种信号分子，至少部分地通过激活外排泵来增加细菌的抗生素抗性。所述的表达根瘤农杆菌的acrA转录物也由吲哚可诱导以剂量依赖的方式。吲哚诱导了针对CIP，NAL和SDS的保护，但增强了对NOV和TRI的敏感性。另外，根癌农杆菌的TET抗性显然不受吲哚调节。根癌农杆菌AcrAB起主要作用，是耐受高水平有毒化合物所必需的。了解多药外排泵的调节以及细菌对细胞内和细胞外信号分子的耐药性适应性反应至关重要。该信息将有助于合理设计有效的细菌感染治疗方法，以克服可能的耐多药病原体。