Conformational changes in the AdeB transmembrane efflux pump protein by amphiphilic peptide Mastoparan-B, down-regulates expression of the adeB Gene and restores antibiotics Susceptibility.
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 MICs against 12 antibiotics as well as MP-B. Expression of the adeB gene in the presence and absence of sub-MIC of MP-B was studied by qRT-PCR. It was found that MP-B had potent antimicrobial activity (MIC=1 g/ml) associated with a 20-fold decrease in the adeB gene expression at the sub-MIC level. The stereochemical analysis using several automated servers confirmed that the AdeB protein 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. Furthermore, 20 ligands were generated from the initial docked poses to create the correct protein-peptide complexes using the BioLiP pipeline. The pose showed high Z=1.2, C=1.41, TM=0.99, and RMSD=4.4 scores was selected for docking purposes. The molecular docking via AutoDock/Vina revealed that MP-B form H-bound with Val 499, Phe 454, Thr 474, Ser 461, Gly 465, and Tyr 468 residues of the AdeB helix-5 and caused a shift in the dihedral angle ({Phi}/{Psi}) by distances of 9.0 [A], 9.3 [A], and 9.6 [A], respectively. This shift in folding was detected by AlphaFold 2 and influenced the overall druggability of the protein. From the above results, we concluded that MP-B can be a good candidate for bacterial efflux pump inhibition.