Volume 25, Issue 3 (5-2021)                   IBJ 2021, 25(3): 193-201 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Kandehkar-Ghahraman M R, Hosseini-Nave H, Azizi O, Shakibaie M R, Mollaie H, Shakibaie S. Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate. IBJ 2021; 25 (3) :193-201
URL: http://ibj.pasteur.ac.ir/article-1-3287-en.html
Stereochemical Trajectories of a Two-Component Regulatory System PmrA/B in a Colistin-Resistant Acinetobacter baumannii Clinical Isolate
Mohammad Reza Kandehkar-Ghahraman , Hossein Hosseini-Nave , Omid Azizi , Mohammad Reza Shakibaie * , Hamid Mollaie , Samane Shakibaie
Abstract:  
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.
Keywords: Acinetobacter baumannii, Amino acid substitution, Colistin, Mutation
Full-Text [PDF 1802 kb]      
Type of Study: Full Length/Original Article | Subject: Molecular Microbiology
References
1. Geisinger E, Huo W, Hernandez-Bird J, Isberg RR. Acinetobacter baumannii: Envelope determinants that control drug resistance, virulence, and surface variability. Annual review of microbiology 2019; 73: 481-506. [DOI:10.1146/annurev-micro-020518-115714]
2. Carretero-Ledesma M, García-Quintanilla M, Martín-Peña R, Pulido MR, Pachón J, McConnell MJ. Phenotypic changes associated with colistin resistance due to lipopolysaccharide loss in Acinetobacter baumannii. Virulence 2018; 9(1): 930-942. [DOI:10.1080/21505594.2018.1460187]
3. Jiang X, Yang K, Han ML, Yuan B, Li J, Gong B, Velkov T, Schreiber F, Wang L, Li J. Outer membranes of polymyxin-resistant Acinetobacter baumannii with phosphoethanolamine-modified lipid A and lipopolysaccharide loss display different atomic-scale interactions with polymyxin. ACS infectious diseases 2020; 10: 2698-2708. [DOI:10.1021/acsinfecdis.0c00330]
4. Olaitan A, Morand S, Rolain JM. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria. Frontiers in Microbiology 2014; 5: 643. [DOI:10.3389/fmicb.2014.00643]
5. Mäkelä PH, Sarvas M, Calcagno S, Lounatmaa K. Isolation and genetic characterization of polymyxin-resistant mutants of Salmonella. FEMS microbiology letters 1978; 3(6): 323-26. [DOI:10.1111/j.1574-6968.1978.tb01963.x]
6. Zhou Z, Ribeiro A, Lin S, Cotter R, Miller S, Raetz C. Lipid A modifications in polymyxin-resistant Salmonella Typhimurium: PmrA-dependent 4-amino-4-deoxy-L-arabinose, and phosphoethanolamine incorporation. Journal of biological chemistry 2001; 276(46): 43111-43121. [DOI:10.1074/jbc.M106960200]
7. Beceiro A, Llobet E, Aranda J, Bengoechea J, Doumith M, Hornsey M, Dhanji H, Chart H, Bou G, Livermore DM, Woodford N. Phosphoethanolamine modification of lipid A in colistin-resistant variants of Acinetobacter baumannii mediated by the PmrA/B two-component regulatory system. Antimicrobial agents and chemotherapy 2011; 55(7): 3370-3379. [DOI:10.1128/AAC.00079-11]
8. Cai Y, Chai D, Wang R, Liang B, Bai N. Colistin resistance of Acinetobacter baumannii: Clinical reports, mechanisms and antimicrobial strategies. Journal of antimicrobial chemotherapy 2012; 67: 1607-1615. [DOI:10.1093/jac/dks084]
9. Casino P, Rubio V, Marina A. Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction. Cell 2009; 139(2): 325-336. [DOI:10.1016/j.cell.2009.08.032]
10. Lesho E, Yoon E, McGann P, Snesrud E, Kwak Y, Milillo M, Onmus-Leone F, Preston L, St Clair K, Nikolich M, Viscount H, Wortmann G, Zapor M, Grillot-Courvalin C, Courvalin P, Clifford R, Waterman PE. Emergence of colistin-resistance in extremely drug-resistant Acinetobacter baumannii containing a novel pmrCAB operon during colistin therapy of wound infections. Journal of infectious diseases 2013; 208(7): 1142-1151. [DOI:10.1093/infdis/jit293]
11. Lee H, Hsu F, Turk J, Groisman E. The PmrA regulated pmrC gene mediates phosphoethanolamine modification of lipid A and polymyxin resistance in Salmonella enterica. Journal of bacteriology 2004; 186 (13): 4124-4133. [DOI:10.1128/JB.186.13.4124-4133.2004]
12. Bhagirath A, Li Y, Patidar R, Yerex K, Ma X, Kumar A, Duan K. Two component regulatory systems and antibiotic resistance in Gram-negative pathogens. International journal of molecular sciences 2019; 20(7): 1781. [DOI:10.3390/ijms20071781]
13. Lou YC, Weng TH, Li YC, Kao YF, Lin WF, Peng HL, Chou SH, Hsiao CD, Chen C. Structure and dynamics of polymyxin-resistance-associated response regulator PmrA in complex with promoter DNA. Nature communications 2015; 6: 8838. [DOI:10.1038/ncomms9838]
14. Huang J, Li C, Song J, Velkov T, Wang L, Zhu Y, Li J. Regulating polymyxin resistance in Gram-negative bacteria: Roles of two-component systems PhoPQ and PmrAB. Future microbiology 2020; 15(6): 445-459. [DOI:10.2217/fmb-2019-0322]
15. Arroyo LA, Herrera CM, Fernandez L, Hankins JV, Trent MS, Hancock RE. The pmrCAB operon mediates polymyxin resistance in Acinetobacter baumannii ATCC 17978 and clinical isolates through phosphoethanolamine modification of Lipid A. Antimicrobial agents and chemotherapy 2011; 55(8): 3743-3751. [DOI:10.1128/AAC.00256-11]
16. Ghahraman KMR, Hosseini-Nave H, Azizi O, Shakibaie MR, Mollaie H, Shakibaie S. Molecular characterization of lpxACD and pmrA/B two-component regulatory system in the colistin resistance Acinetobacter baumannii clinical isolates. Gene reports 2020; 21:100952. [DOI:10.1016/j.genrep.2020.100952]
17. Shakibaie MR, Azizi O, Shahcheraghi F. Insight into stereochemistry of a new IMP allelic variant (IMP-55) metallo-β-lactamase identified in a clinical strain of Acinetobacter baumannii. Infection, genetics and evolution 2017; 51: 118-126. [DOI:10.1016/j.meegid.2017.03.018]
18. Gerson S, Betts JW, Lucaßen K, Nodari CS, Wille J, Josten M, Göttig S, Nowak J, Stefanik D, Roca I, Vila J, Cisneros JM, La Ragione RM, Seifert H, Higgins PG. Investigation of novel pmrB and EptA mutations in isogenic Acinetobacter baumannii isolates associated with colistin resistance and increased virulence in vivo. Antimicrobial agents and chemotherapy 2019; 63(3): e01586-18. [DOI:10.1128/AAC.01586-18]
19. Schwede T, Kopp T, Guex N, Peitsch M. SWISS-MODEL: An automated protein homology-modeling server. Nucleic acids research 2003; 31:3381-3385. [DOI:10.1093/nar/gkg520]
20. Biasini M, Schmidt T, Bienert S, Mariani V, Studer G, Haas J, Johner N, Schenk A.D, Philippsen A, Schwede T. Open Structure: An integrated software framework for computational structural biology. Acta crystallographic, section D, biological crystallography 2013; 69(Pt 5): 701-709. [DOI:10.1107/S0907444913007051]
21. Jones D: Protein secondary structure prediction based on position-specific scoring matrices. Journal of molecular miology 1999; 292(2): 195-202. [DOI:10.1006/jmbi.1999.3091]
22. Haddad Y, Adam V, Heger Z. Ten quick tips for homology modeling of high-resolution protein 3D structures. PLoS computational biology 2020; 16(4): e1007449. [DOI:10.1371/journal.pcbi.1007449]
23. Deng L, Zhong G, Liu C, Luo J, Liu H. MADOKA: An ultra-fast approach for large-scale protein structure similarity searching. BMC bioinformatics 2019; 20 (Suppl 19): 662. [DOI:10.1186/s12859-019-3235-1]
24. Kufareva I, Abagyan R. Methods of protein structure comparison. Methods in molecular biology 2012; 857: 231-257. [DOI:10.1007/978-1-61779-588-6_10]
25. Xiong J. Essential Bioinformatics. United Kingdaom: Cambridge: Cambridge University Press; 2006.
26. Redfern OC, Harrison A, Dallman T, Pearl FMG, Orengo CA. CATHEDRAL: A fast and effective algorithm to predict folds and domain boundaries from multidomain protein structures. PLoS computational biology 2007; 3(11): e232. [DOI:10.1371/journal.pcbi.0030232]
27. Dago A, Schug A, Procaccini A, Hoch J, Weigt M, Szurmant H. Structural basis of histidine kinase autophosphorylation deduced by integrating genomics, molecular dynamics, and mutagenesis. Proceedings of the national academy of sciences of the United States of America 2012; 109(26): E1733-1742. [DOI:10.1073/pnas.1201301109]
28. Dutta R, Inouye M. GHKL. An emergent ATPase/kinase superfamily. Trends in biochemical science 2000; 25(1): 24-28. [DOI:10.1016/S0968-0004(99)01503-0]
29. Marina A, Waldburger C, Hendrickson W. Structure of the entire cytoplasmic portion of a sensor histidine-kinase protein. EMBO Journal 2005; 24(24): 4247-4259. [DOI:10.1038/sj.emboj.7600886]
30. Casino P, Miguel-Romero L, Marina A. Visualizing autophosphorylation in histidine kinases. Nature communications 2014; 5: 3258. [DOI:10.1038/ncomms4258]
31. Sun B, Liu H, Jiang Y, Shao L, Yang S, Chen D. New mutations involved in colistin resistance in Acinetobacter baumannii. mSphere 2020;5: e00895-19 [DOI:10.1128/mSphere.00895-19]
32. Dutta R, Qin L, Inouye M. Histidine kinases: Diversity of domain organization. Molecular microbiology 1999; 34(4): 633-640. [DOI:10.1046/j.1365-2958.1999.01646.x]
Add your comments about this article : Your username or Email:
CAPTCHA
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb