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Resistance to vancomycin (VAN) is increasing at an alarming rate. Resurrecting antibiotics using a combination approach is a promising alternative avenue. Galangin (GAL) is a bioactive compound constituted in herbal plants. This study aimed to evaluate the synergistic activity of the combination of GAL and VAN and mode of action against vancomycin-resistant E. faecium (VREfm) strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>The minimal inhibitory concentrations against these bacteria were 8\u201364\u00a0\u03bcg ml\u22121 for VAN and 512\u00a0\u03bcg ml\u22121 for GAL. The VAN plus GAL combination exhibited synergistic effects against E. faecium isolates, with a fraction inhibitory concentration index of 0.26\u20130.28. Time-kill assays confirmed this synergism. Mechanistic studies showed that the combination induced intracellular constituent leakage, suggesting impaired membrane permeability and electron microscopy revealed peptidoglycan and membrane damage. Additionally, the GAL plus VAN combination inhibited biofilm formation and significantly reduced lipid, protein, and carbohydrate contents, as shown by Fourier-transform infrared spectroscopy (FTIR).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>GAL could reverse the activity of VAN against VREfm by damaging bacterial cell envelope, inhibiting biofilm formation, and reducing biomolecule contents, emphasizing its potential as a valuable adjunct to VAN in treating VREfm infections.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jambio\/lxaf011","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T02:27:32Z","timestamp":1736389652000},"source":"Crossref","is-referenced-by-count":5,"title":["Galangin synergistically revives the antibacterial activity of vancomycin against vancomycin-resistant <i>Enterococcus faecium<\/i>"],"prefix":"10.1093","volume":"136","author":[{"given":"Intu-orn","family":"Ayamuang","sequence":"first","affiliation":[{"name":"School of Biology, Institute of Science, Suranaree University of Technology , University Avenue, Muang District, Nakhon Ratchasima 30000 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yothin","family":"Teethaisong","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Faculty of Allied Health Sciences, Burapha University , Longhaad Bangsaen Road, Muang District, Chon Buri 20131 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kittipot","family":"Sirichaiwetchakoon","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Burapha University , Longhaad Bangsaen Road, Muang District, Chonburi 20131 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siriporn","family":"Suknasang","sequence":"additional","affiliation":[{"name":"School of Preclinical Sciences, Institute of Science, Suranaree University of Technology , University Avenue, Muang District, Nakhon Ratchasima 30000 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santi","family":"Watthana","sequence":"additional","affiliation":[{"name":"School of Biology, Institute of Science, Suranaree University of Technology , University Avenue, Muang District, Nakhon Ratchasima 30000 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yupaporn","family":"Chaiseha","sequence":"additional","affiliation":[{"name":"School of Biology, Institute of Science, Suranaree University of Technology , University Avenue, Muang District, Nakhon Ratchasima 30000 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Griangsak","family":"Eumkeb","sequence":"additional","affiliation":[{"name":"School of Preclinical Sciences, Institute of Science, Suranaree University of Technology , University Avenue, Muang District, Nakhon Ratchasima 30000 ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"2025013014344851600_bib1","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1089\/mdr.2017.0147","article-title":"Vancomycin-resistant enterococci: a review of antimicrobial resistance mechanisms and perspectives of human and animal health","volume":"24","author":"Ahmed","year":"2018","journal-title":"Microb Drug Resist"},{"key":"2025013014344851600_bib2","doi-asserted-by":"publisher","first-page":"8992","DOI":"10.1021\/jf801604p","article-title":"Using fourier transform infrared (FT-IR) absorbance spectroscopy and multivariate analysis to study the effect of chlorine-induced bacterial injury in water","volume":"56","author":"Al-Qadiri","year":"2008","journal-title":"J Agric Food Chem"},{"key":"2025013014344851600_bib3","doi-asserted-by":"publisher","first-page":"124","DOI":"10.4314\/ajtcam.v11i3.19","article-title":"Antibacterial and anti-biofilm activity of flavonoids and triterpenes isolated from the extracts of Ficus sansibarica Warb. 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