| Summary: | Healthcare-associated methicillin-resistant <i>Staphylococcus aureus</i> infections represent extremely high morbidity and mortality rates worldwide. We aimed to assess the antimicrobial potential and synergistic effect between Epigalocatenin-3-gallate (EGCG) and different antibiotics in <i>S. aureus</i> strains with divergent resistance phenotypes. EGCG exposure effects in epigenetic and drug resistance key modulators were also evaluated. <i>S. aureus</i> strains (<i>n</i> = 32) were isolated from infected patients in a Lisbon hospital. The identification of the <i>S. aureus</i> resistance phenotype was performed through automatized methods. The antibiotic synergistic assay was performed through disk diffusion according to EUCAST guidelines with co-exposure to EGCG (250, 100, 50 and 25 µg/mL). The bacteria’s molecular profile was assessed through FTIR spectroscopy. The transcriptional expression of <i>OrfX</i>, <i>SpdC</i> and <i>WalKR</i> was performed by using qRT-PCR. FTIR-spectroscopy analysis enabled the clear discrimination of MRSA/MSSA strains and the EGCG exposure effect in the bacteria’s molecular profiles. Divergent resistant phenotypes were associated with divergent transcriptional expression of the epigenetic modulator <i>OrfX</i>, particularly in MRSA strains, as well as the key drug response modulators <i>SpdC</i> and <i>WalKR</i>. These results clearly demonstrate that EGCG exposure alters the expression patterns of key epigenetic and drug response genes with associated divergent-resistant profiles, which supports its potential for antimicrobial treatment and/or therapeutic adjuvant against antibiotic-resistant microorganisms.
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