Abstract
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.
Highlights
The resistance with efflux pump of the RND (Resistance-Nodulation-Division) superfamily are found ubiquitously throughout the Bacteria, Archaea and Eukaryotes
From the most common and important clinical gram negative pathogens that have been reported to be resistant by RND multidrug efflux pumps, the following bacteria were selected based on existing sequence of RND genes in NCBI nucleotide database: 22 Acinetobacter baumannii, 40 Escherichia coli, 19 Klebsiella pneumonia, 11 Proteus mirabilis, 35 Pseudomonas aeruginosa, 10 Serratia marcescens, 15 Stenotrophomonas malto
A highly conserved sequence with 282 base pair long were perceived with alignment main transporter in bacterial species: Escherichia coli, Klebsiella pneumonia, Pseudomonas aeroginosa, Serratia marcescens, Stenotrophomonas maltophilia, Shigella dysenteriae and Shigella sonnei (The conserved area was not found in Acinetobacter baumannii and Proteus mirabilis) (Figure 1)
Summary
The resistance with efflux pump of the RND (Resistance-Nodulation-Division) superfamily are found ubiquitously throughout the Bacteria, Archaea and Eukaryotes. RND efflux pumps (such as AcrB of Escherichia coli and MexB of Pseudomonas aeruginosa) plays a significant role in the innate resistance of Gram-negative bacteria to multiple classes of structurally distinct antimicrobials, including those that are clinically relevant[1, 2]. Those belonging to the RND family play a most important role in resistance of Gram-negative bacteria to a wide range of toxic compounds, including antibiotics, biocides, and heavy metals[3, 4]. The aim of the present study was the accurate analysis the consensus sequence of RND multidrug efflux pumps components genes in the most common and important clinical bacterial species, and study the highly conserved residues in the arrangement of the nucleotide and amino acid sequences and draw a phylogenetic tree
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