Iranian Biomedical Journal

en Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate Molecular Microbiology Molecular Microbiology مقاله کامل Full Length/Original Article Background: There is limited information on the three-dimensional (3D) prediction and modeling of the colistin resistance-associated proteins PmrA/B TCS in Acinetobacter baumannii. We aimed to evaluate the stereochemical structure and domain characterization of phosphotransferase membrane receptor A/B (PmrA/B) in an A. baumannii isolate resistant to high-level colistin, using bioinformatics tools. Methods: The species of the isolate and its susceptibility to colistin were confirmed by PCR-sequencing and minimum inhibitory concentration assay, respectively. For 3D prediction of the PmrA/B, we used 16 template models with the highest quality (e-value <1 × 10−50). Results: Prediction of the PmrA structure revealed a monomeric non-redundant protein consisting of 28 α-helices and 22 β-sheets. The PmrA DNA-binding motif displayed three antiparallel α-helices, followed by three β-sheets, and was bond to the major groove of DNA by intermolecular van der Waals bonds through amino acids Lys, Asp, His, and Arg, respectively. Superimposition of the deduced PmrA 3D structure with the closely related PmrA protein model (GenBank no. WP_071210493.1) revealed no distortion in conformation, due to Glu→Lys substitution at position 218. Similarly, the PmrB protein structure displayed 24 α-helices and 13 β-sheets. In our case, His251 acted as a phosphate receptor in the HisKA domain. The amino acid substitutions were mainly observed at the putative N-terminus region of the protein. Furthermore, two substitutions (Lys21→Ser and Ser28→Arg) in the transmembrane domain were detected. Conclusion: The DNA-binding motif of PmrA is highly conserved, though the N-terminal fragment of PmrB showed a high rate of base substitutions. This research provides valuable insights into the mechanism of colistin resistance in A. baumannii. Acinetobacter baumannii, Amino acid substitution, Colistin, Mutation 193 201 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-4269-1&slc_lang=en&sid=1 Mohammad Reza Kandehkar-Ghahraman mamad_s47@yahoo.com 0000-0001-8274-0384 No Department of Microbiology and Virology, Kerman University of Medical Sciences, Kerman, Iran Hossein Hosseini-Nave hosseini.nave@gmail.com 0000-0002-9152-818X No Department of Microbiology and Virology, Kerman University of Medical Sciences, Kerman, Iran Omid Azizi omid201262@gmail.com 0000-0002-0911-339X No Department of Laboratory Sciences, School of Paramedical Sciences, Torbat Heydariyeh University of Medical sciences, Torbat Heydariyeh, Iran Mohammad Reza Shakibaie mohammadreza.shakibaie@gmail.com 0000-0003-2524-125X Yes Department of Microbiology and Virology, Kerman University of Medical Sciences, Kerman, Iran Hamid Mollaie hmollaie@gmail.com 0000-0001-5115-7495 No Research Center for Tropical and Infectious Diseases Kerman University of Medical Sciences, Kerman, Iran Samane Shakibaie 0000-0002-1517-4551 No Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran