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Conformational changes in the AdeB transmembrane efflux pump by amphiphilic peptide Mastoparan-B, down-regulates expression of the ade B gene and restores antibiotics susceptibility
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  • Mohammad Reza Shakibaie,
  • Farzan Modaresi,
  • Omid Azizi,
  • Omid Tadjrobehkar,
  • Mohammad Mehdi Ghaemi
Mohammad Reza Shakibaie
Kerman University of Medical Sciences

Corresponding Author:[email protected]

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Farzan Modaresi
Jahrom University of Medical Science
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Omid Azizi
Torbat Heydarieh University of Medical Sciences
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Omid Tadjrobehkar
Kerman University of Medical Sciences
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Mohammad Mehdi Ghaemi
Kerman University of Medical Sciences
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Abstract

No report exists on the role of Mastoparan B (MP-B) as an RND efflux pump inhibitor in multi-drug resistant (MDR) Acinetobacter baumannii. Here, we performed a series of in-silico experiments to predict the inhibition of the AdeB efflux pump by MP-B as a drug target agent. For this reason, an MDR strain of A. baumannii was subjected to minimum inhibitory concentration (MIC) against 12 antibiotics as well as MP-B. Expression of the a deB gene in the absence and presence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 µg/ml) associated with a 20-fold decrease in its expression at sub-MIC of MP-B. The stereochemical analysis using several automated servers confirmed that the AdeB is an inner membrane of the RND tripartite complex system with helix-turn-helix conformation and a pore rich in Phe, Ala, and Lys residue. The best model that showed high accuracy (Z=1.2, C=1.41, TM=0.99, and RMSD=4.4) was selected for docking purposes using the Site Map tool, and the correct protein-peptide complexes were simulated in the BioLiP platform. The molecular docking via AutoDock/Vina suggested that MP-B form H-bound with amino acid residues of the AdeB helix-5 and caused a shift in the dihedral angle by distances of 9.0 Å, 9.3 Å, and 9.6 Å, respectively. This shift was detected by the AlphaFold 2 tool and influenced the overall druggability of the protein. From the results, we concluded that, MP-B can be a good candidate for inhibition of bacterial efflux pump.
19 Dec 2022Submitted to PROTEINS: Structure, Function, and Bioinformatics
20 Dec 2022Submission Checks Completed
20 Dec 2022Assigned to Editor
20 Dec 2022Review(s) Completed, Editorial Evaluation Pending
20 Dec 2022Reviewer(s) Assigned
30 Jan 2023Editorial Decision: Revise Major
22 Feb 20231st Revision Received
22 Feb 2023Submission Checks Completed
22 Feb 2023Assigned to Editor
22 Feb 2023Review(s) Completed, Editorial Evaluation Pending
22 Feb 2023Reviewer(s) Assigned
13 Apr 2023Editorial Decision: Revise Major
11 May 20232nd Revision Received
11 May 2023Submission Checks Completed
11 May 2023Assigned to Editor
11 May 2023Review(s) Completed, Editorial Evaluation Pending
11 May 2023Reviewer(s) Assigned
30 May 2023Editorial Decision: Accept