Bacterial Actin MreB as a new antibiotic target

Bódis, Emőke and Longauer, Beáta and Lukács, András and Huber, Tamás and Nyitrai, Miklós and Makkai, Géza and Jánosi, Tibor Z. and Börzsei, Rita and Hetényi, Csaba and Gazdag, Zoltán and Barkó, Szilvia (2026) Bacterial Actin MreB as a new antibiotic target. FRONTIERS IN MOLECULAR BIOSCIENCES. ISSN 2296-889X (In Press)

Text 1912759_Manuscript.pdf - Accepted Version Available under License Creative Commons Attribution. Download (1MB)

Abstract

Actin homologue MreB has a crucial role in the synthesis of the bacterial cell wall. Disruption of the MreB filament network results in the disruption of the cell wall, which serves thus an unconventional antibacterial strategy. A22, a small inhibitor molecule binds directly to the MreB filament altering its structure causing a morphological change of the cell, leading to cell death. This effective antibacterial property is shadowed by the fact that at high concentration A22 is toxic to the eukaryotic host cells, so it cannot be administered at higher doses. Vancomycin is a widely used antibiotic targeting the Gram-positive bacteria at concentrations as high as 10–20 μg/ml, which can occasionally cause serious side effects. Here, we present our recent findings that a synergistic interaction exists between A22 and vancomycin, which results in the inhibition of cell proliferation by the combined use of very low concentrations of A22 (6.25 μg/ml) and vancomycin (1.56 μg/ml). In addition, in the presence of A22, vancomycin is effective not only against Gram-positive bacteria, but also against Gram-negative bacteria. Since five of the seven most common antibiotic-resistant bacteria according to the WHO are Gram-negative, this synergism between A22 and vancomycin opens a new way combating bacterial infections. Our spectroscopic results prove support that vancomycin binds directly to MreB; using computer docking method we determined the possible binding site of vancomycin on MreB filament. This newly identified interaction between vancomycin and A22 highlights the potential of the combined use opening a new strategy to tackle antibiotic resistance. Summary Keywords

Actions (login required)

View Item