Shahini Shams Abadi Milad, Gholipour Abolfazl, Hadi Nahal
Department of Bacteriology & Virology, School of medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Cell Mol Biol (Noisy-le-grand). 2018 Oct 30;64(13):79-83.
RND (Resistance-Nodulation-Division) family transporters have a vital role in both intrinsic and acquired multi-drug resistance in Gram-negative bacteria. It is important to find a conserved domain in the RND family between different pathogenic bacteria for diagnostic and therapeutic purpose. Total sequences of three-component system RND efflux pumps were retrieved from NCBI nucleotide and protein database and were subjected to conservation and variation analysis using the multiple sequence alignment feature of the CLC workbench. The phylogenetic tree for main transporters was drawn and the three-dimensional structure was also evaluated. From the sequence conservation analysis, highly conserved residues with 282 base pair (94 amino acid) long were identified. The location of the highly conserved domain is positioned in the domain 1 crystallographic structure of AcrB Escherichia coli and MexB Pseudomonas aeruginosa. The main transporter component phylogenetic tree shows the clusters of different genotypes and their evolutionary association. Each of three components of RND proteins is crucial for drug efflux, and the absence of even one component makes the entire complex totally nonfunctional. Therefore, this highly conserved region can be used to disable the RND multidrug efflux pumps. In addition, this highly conserved can also be used for diagnostic aspects.
RND（抗性-结瘤-分裂）家族转运蛋白在革兰氏阴性菌的固有和获得性多药耐药中起着至关重要的作用。为了诊断和治疗目的，在不同病原菌的RND家族中找到一个保守结构域很重要。从NCBI核苷酸和蛋白质数据库中检索出三组分系统RND外排泵的完整序列，并使用CLC工作台的多序列比对功能进行保守性和变异性分析。绘制了主要转运蛋白的系统发育树，并对三维结构进行了评估。通过序列保守性分析，鉴定出了长度为282个碱基对（94个氨基酸）的高度保守残基。高度保守结构域的位置位于大肠杆菌AcrB和铜绿假单胞菌MexB的1结构域晶体结构中。主要转运蛋白组分系统发育树显示了不同基因型的聚类及其进化关联。RND蛋白的三个组分中的每一个对于药物外排都至关重要，即使缺少一个组分也会使整个复合物完全失去功能。因此，这个高度保守区域可用于使RND多药外排泵失活。此外，这个高度保守区域也可用于诊断方面。
