Multitarget Mechanisms of (‒)‒Epigallocatechin-3-Gallate Against MRSA: From SraP L-Lectin Targeting to Synergistic Antibiotic Effects

TL;DR

This study shows that EGCG, a natural compound, fights MRSA by targeting a key protein and working well with antibiotics.

Contribution

The study reveals EGCG's multitarget mechanism against MRSA, including SraP L-Lectin targeting and synergistic antibiotic effects.

Findings

EGCG binds to SraP L-Lectin with high affinity and inhibits MRSA colonization.

EGCG suppresses pyrimidine metabolism and downregulates genes related to bacterial growth and β-lactam resistance.

Combining EGCG with ceftriaxone significantly reduces the required antibiotic dosage and prolongs its effect.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA), a major global public health threat due to its broad resistance, urgently requires the development of new antibiotic alternatives. (‒)‒Epigallocatechin-3-gallate (EGCG) is considered a natural bioactive compound with anti-MRSA properties. The L-Lectin module of serine-rich adhesin for platelets (SraP) is considered an important target for blocking MRSA-infected hosts. This study aims to investigate the mechanism of action of EGCG against MRSA. Surface plasmon resonance (SPR), cell adhesion and invasion, biofilm formation, checkerboard assays, RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The results showed that EGCG bound to SraP L Lectin with high affinity and effectively inhibited MRSA colonization. Additionally, EGCG significantly suppressed pyrimidine metabolism and downregulated related genes, thereby potentially inhibiting bacterial growth. It also markedly reduced the expression of multiple genes associated with β-lactam resistance and inhibited biofilm formation. A strong synergistic effect was observed between EGCG and the bactericidal agent ceftriaxone (CRO). When combined with 10 μg/mL EGCG, CRO required 75% less dosage and exhibited a prolonged antimicrobial effect. In conclusion, EGCG exerts anti-MRSA effects through multiple pathways and represents a promising candidate as an alternative therapeutic agent against MRSA infections.

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