AccScience Publishing / IMO / Online First / DOI: 10.36922/IMO026160018
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ORIGINAL RESEARCH ARTICLE

Epicatechin gallate disrupts methicillin resistant Staphylococcus aureus cell envelope integrity and enhances antibiotic activity

Sze-Tieng Ang1 ,  Matthew James Cheesman2 ,  Tak Kim1 ,  Ian Edwin Cock1*
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1 School of Environmental and Science, Griffith University, Nathan Campus, Brisbane, Queensland, Australia
2 School of Pharmacy and Medical Sciences, Griffith University, Gold Coast Campus, Southport, Queensland, Australia
IMO, 026160018 https://doi.org/10.36922/IMO026160018
Received: 16 April 2026 | Revised: 8 June 2026 | Accepted: 9 June 2026 | Published online: 23 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) highlights the need for alternative therapeutic strategies. Natural product-derived resistance-modifying compounds are gaining attention as antibiotic adjuvants to restore drug activity. Epicatechin gallate (EPCG) has antibacterial and anti-virulence properties. This study investigates the antibacterial activity of EPCG and its potential to enhance the efficacy of selected antibiotics against S. aureus and MRSA. Standard broth microdilution assays were used to determine the minimum inhibitory concentration (MIC) of EPCG against S. aureus and MRSA. Synergistic interactions with selected antibiotics were evaluated using checkerboard and isobologram assays. Furthermore, cytotoxicity was evaluated using Artemia franciscana nauplii (brine shrimp) lethality and human dermal fibroblast (HDF) assays. The impact of EPCG, cefotaxime, and their combinations on cells and biofilms was visualised through confocal and cryo-electron microscopy. EPCG demonstrated strong antibacterial activity (MIC = 208 μg/mL against S. aureus and 188 μg/mL against MRSA). Isobologram assays also revealed strong synergy for the EPCG–cefotaxime combination (Σ fractional inhibitory concentration = 0.15 for MRSA; 0.25 for S. aureus). EPCG exhibited moderate toxicity toward HDF cells (LC50 = 100 μg/mL), whereas the optimised cefotaxime: EPCG (90:10 [v/v]) combination was non-toxic across all assays. Additionally, confocal microscopy revealed reduced bacterial aggregation and diminished biofilm-associated fluorescence following EPCG treatment. Cryo-electron microscopy revealed pronounced ultrastructural disruptions in MRSA cells treated with the combination. In conclusion, EPCG enhances the antibacterial activity of antibiotics such as cefotaxime against S. aureus and MRSA. Its synergistic action, lower cytotoxicity at optimal ratios, and confirmed damage to bacterial cells highlight EPCG’s potential as a natural antibiotic adjuvant.

Keywords
Methicillin-resistant Staphylococcus aureus
Epicatechin gallate
Minimum inhibitory concentration
Synergy
Confocal microscopy
Cryo-electron microscopy
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Innovative Medicines & Omics, Electronic ISSN: 3060-8740 Print ISSN: 3060-8910, Published by AccScience Publishing
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