{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:01:09Z","timestamp":1790834469217,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Actin homolog MreB plays 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 thus serves an unconventional antibacterial strategy. A22, a small inhibitor molecule, binds directly to the MreB filament, altering its structure and 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 eukaryotic host cells, so it cannot be administered at higher doses. Vancomycin is a widely used antibiotic targeting Gram-positive bacteria at concentrations as high as 10\u201320 \u03bcg\/mL, which can occasionally cause serious side effects. In this study, 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 \u03bcg\/mL) and vancomycin (1.56 \u03bcg\/mL). In addition, in the presence of A22, vancomycin is effective not only against Gram-positive bacteria but also against Gram-negative bacteria. Since 5 of the 7 most common antibiotic-resistant bacteria according to the WHO are Gram-negative, this synergism between A22 and vancomycin opens a new way of combating bacterial infections. Our spectroscopic results indicate that vancomycin binds directly to MreB; using a computer docking method, we determined the possible binding site of vancomycin on the MreB filament. This newly identified interaction between vancomycin and A22 highlights the potential of the combined use, providing a new strategy to tackle antibiotic resistance.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1912759","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:49Z","timestamp":1790833309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacterial actin MreB as a new antibiotic target"],"prefix":"10.3389","volume":"13","author":[{"given":"Em\u0151ke","family":"B\u00f3dis","sequence":"first","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"Longauer","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s","family":"Luk\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikl\u00f3s","family":"Nyitrai","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9za","family":"Makkai","sequence":"additional","affiliation":[{"name":"Nano-Bio-Imaging Core Facility, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tibor","family":"J\u00e1nosi","sequence":"additional","affiliation":[{"name":"Nano-Bio-Imaging Core Facility, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"B\u00f6rzsei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Pharmacoinformatics Unit Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Het\u00e9nyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Pharmacoinformatics Unit Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Gazdag","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology Faculty of Sciences, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilvia","family":"Bark\u00f3","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Medical School, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B2","doi-asserted-by":"publisher","first-page":"884","DOI":"10.3389\/fchem.2019.00884","article-title":"Status of targeting MreB for the development of antibiotics","volume":"7","author":"Awuni","year":"2020","journal-title":"Front. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"9867","DOI":"10.1021\/acs.jpcb.6b05199","article-title":"Exploring the A22-Bacterial actin MreB interaction through molecular dynamics simulations","volume":"120","author":"Awuni","year":"2016","journal-title":"J. Phys. Chem. B"},{"key":"B4","doi-asserted-by":"publisher","first-page":"4852","DOI":"10.1021\/bi900014d","article-title":"A22 disrupts the bacterial actin cytoskeleton by directly binding and inducing a low-affinity state in MreB","volume":"48","author":"Bean","year":"2009","journal-title":"Biochemistry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.micpath.2016.07.007","article-title":"Antibacterial, cyto and genotoxic activities of A22 compound ((S-3, 4 -dichlorobenzyl) isothiourea hydrochloride)","volume":"99","author":"Bonez","year":"2016","journal-title":"Microb. Pathog."},{"key":"B7","doi-asserted-by":"publisher","first-page":"238","DOI":"10.3390\/antibiotics9050238","article-title":"Toxic effect of vancomycin on viability and functionality of different cells involved in tissue regeneration","volume":"9","author":"Braun","year":"2020","journal-title":"Antibiot. (Basel)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"693","DOI":"10.3390\/ANTIBIOTICS11050693","article-title":"TXH11106: a third-generation MreB inhibitor with enhanced activity against a broad range of gram-negative bacterial pathogens","volume":"11","author":"Bryan","year":"2022","journal-title":"Antibiotics"},{"key":"B9","volume-title":"Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically: M07-A10; Approved Standard","year":"2015"},{"key":"B10","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/35092500","article-title":"Prokaryotic origin of the actin cytoskeleton","volume":"413","author":"Ent","year":"2001","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7554\/eLife.02634","article-title":"Bacterial actin MreB forms antiparallel double filaments","volume":"2014","author":"Ent","year":"2014","journal-title":"eLife"},{"key":"B12","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1177\/10915818231216413","article-title":"In vitro evaluation of vancomycin-induced toxicity in human primary knee chondrocytes","volume":"43","author":"Hall","year":"2024","journal-title":"Int. J. Toxicol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1002\/jcc.20634","article-title":"A semiempirical free energy force field with charge-based desolvation","volume":"28","author":"Huey","year":"2007","journal-title":"J. Comput. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/08998280.2001.11927763","article-title":"Recommendations for monitoring serum vancomycin concentrations","volume":"14","author":"James","year":"2001","journal-title":"Proc. Bayl Univ. Med. Cent."},{"key":"B15","doi-asserted-by":"publisher","first-page":"67","DOI":"10.4167\/jbv.2015.45.2.67","article-title":"Glycopeptide antibiotics: structure and mechanisms of action","volume":"45","author":"Kang","year":"2015","journal-title":"J. Bacteriol. Virol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1111\/j.1469-0691.2005.01306.x","article-title":"Monitoring of vancomycin serum levels for the treatment of staphylococcal infections","volume":"12","author":"Kitzis","year":"2006","journal-title":"Clin. Microbiol. Infect."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e3057754","DOI":"10.1155\/2021\/3057754","article-title":"Synergistic antibacterial and antibiofilm activity of the MreB inhibitor A22 hydrochloride in combination with conventional antibiotics against Pseudomonas aeruginosa and Escherichia coli clinical isolates","volume":"2021","author":"Kotzialampou","year":"2021","journal-title":"Int. J. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"179124","DOI":"10.1016\/j.scitotenv.2025.179124","article-title":"Spread of antimicrobial-resistant clones of the ESKAPEE group: from the clinical setting to hospital effluent","volume":"973","author":"Krul","year":"2025","journal-title":"Sci. Total Environ."},{"key":"B19","volume-title":"Probing the Molecular Interactions of A22 with Prokaryotic Actin Mreb and Eukaryotic Actin: A Computational and Experimental Study","author":"Kumar","year":"2024"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6717","DOI":"10.1128\/jb.174.21.6717-6728.1992","article-title":"Identification of Bacillus subtilis genes for septum placement and shape determination","volume":"174","author":"Levin","year":"1992","journal-title":"J. Bacteriol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"16044","DOI":"10.3390\/ijms232416044","article-title":"Solubility and thermal stability of Thermotoga maritima MreB","volume":"23","author":"Longauer","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B22","first-page":"21","article-title":"Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American society of health-system pharmacists, the infectious diseases society of America, and the society of infectious diseases pharmacists","volume":"31","author":"Martin","year":"2010","journal-title":"Clin. Biochem. Rev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"17629","DOI":"10.1038\/s41598-017-17772-6","article-title":"Increasing the permeability of Escherichia coli using MAC13243","volume":"7","author":"Muheim","year":"2017","journal-title":"Sci. Rep."},{"key":"B25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ijantimicag.2011.08.015","article-title":"In vitro activity of S-(3,4-dichlorobenzyl)isothiourea hydrochloride and novel structurally related compounds against multidrug-resistant bacteria, including Pseudomonas aeruginosa and Burkholderia cepacia complex","volume":"39","author":"Nicholson","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B26","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3109\/13693786.2013.828160","article-title":"Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations","volume":"52","author":"Nyilasi","year":"2014","journal-title":"Med. Mycol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"793","DOI":"10.3390\/antibiotics9110793","article-title":"Vancomycin serum concentration after 48 h of administration: a 3-Years survey in an intensive care unit","volume":"9","author":"Perin","year":"2020","journal-title":"Antibiotics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1679","DOI":"10.1007\/s00044-022-02967-y","article-title":"Novel MreB inhibitors with antibacterial activity against gram (-) bacteria","volume":"31","author":"Sagong","year":"2022","journal-title":"Review"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1016\/s0969-2126(96)00156-6","article-title":"Crystal structure of vancomycin","volume":"4","author":"Sch\u00e4fer","year":"1996","journal-title":"Structure"},{"key":"B30","volume-title":"The PyMOL Molecular Graphics System, Version 1.8","author":"Schr\u00f6dinger","year":"2015"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00894-012-1667-x","article-title":"Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters","volume":"19","author":"Stewart","year":"2013","journal-title":"J. Mol. Model"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/ncomms4442","article-title":"The actin homologue MreB organizes the bacterial cell membrane","volume":"5","author":"Strahl","year":"2014","journal-title":"Nat. Communications"},{"key":"B33","doi-asserted-by":"publisher","first-page":"6729","DOI":"10.1128\/jb.174.21.6729-6742.1992","article-title":"The divIVB region of the Bacillus subtilis chromosome encodes homologs of Escherichia coli septum placement (minCD) and cell shape (mreBCD) determinants","volume":"174","author":"Varley","year":"1992","journal-title":"J. Bacteriol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.tim.2011.11.004","article-title":"MreB: pilot or passenger of cell wall synthesis?","volume":"20","author":"White","year":"2012","journal-title":"Trends Microbiol."},{"key":"B35","volume-title":"The Selection and Use of Essential Medicines, 2025: WHO Model List of Essential Medicines, 24th List","year":"2025"}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1912759\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:41:52Z","timestamp":1790833312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1912759\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":34,"alternative-id":["10.3389\/fmolb.2026.1912759"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1912759","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"article-number":"1912759"}}