The increase in the antimicrobial resistance (AMR) of Staphylococcus aureus (S. aureus) has become a global public health concern. This study globally monitored the large-scale longitudinal trend of AMR in S. aureus and examined the various human and environmental climate factors that influence the occurrence and spread of AMR in S. aureus, which might provide valuable data to support the development of a global surveillance system for S. aureus AMR and provide a theoretical basis for coordinated actions to control the emergence and development of AMR from multiple perspectives. There was a significantly positive correlation between the number of antibiotic resistance genes (ARGs) in S. aureus and the collection year, with a sharp increase in ARGs over time. The number of ARGs in S. aureus genomes significantly increased each decade, with the average number of ARGs per genome rising from 10.37 ± 3.55 before 1990 to 12.75 ± 4.04 after 2010, suggesting a growing problem of S. aureus AMR. The Spearman correlation results indicated that the human development index (HDI), antibiotic consumption, and mobile genetic elements (MGEs) were significantly associated with the AMR of S. aureus, and these factors played a crucial role in the emergence and development of S. aureus AMR. The results of structural equation modeling showed that the HDI significantly promoted an increase in antibiotic consumption, thereby indirectly enhancing the AMR of S. aureus. Antibiotic consumption also indirectly facilitated the progression of AMR in S. aureus through its impact on MGEs. The results of restricted cubic spline and generalized linear models showed that climate change also played a significant role in the progression of S. aureus AMR. In summary, this study provides a theoretical framework for monitoring the longitudinal trend of ARGs in S. aureus isolates and examining the possible influencing variables of ARGs in these isolates.

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.