Increased Activity of β-Lactam Antibiotics in Combination with Carvacrol against MRSA Bacteremia and Catheter-Associated Biofilm Infections

作者：Jianguo Li, Xiaofeng Chen, Ting-Yin Lu, Jing Zhang, Shu-He Dai, Jian Sun, Ya-Hong Liu, Xiao‐Ping Liao, Yu‐Feng Zhou · 发表于：ACS Infectious Diseases · 年份：2023 · DOI：10.1021/acsinfecdis.3c00338 · 被引用次数：15 · 研究领域：Antimicrobial Resistance in Staphylococcus、Bacterial biofilms and quorum sensing、Antibiotic Resistance in Bacteria

β-Lactam antibiotics are the mainstay for the treatment of staphylococcal infections, but their utility is greatly limited by the emergence and rapid dissemination of methicillin-resistant Staphylococcus aureus (MRSA). Herein, we evaluated the ability of the plant-derived monoterpene carvacrol to act as an antibiotic adjuvant, revitalizing the anti-MRSA activity of β-lactam antibiotics. Increased susceptibility of MRSA to β-lactam antibiotics and significant synergistic activities were observed with carvacrol-based combinations. Carvacrol significantly inhibited MRSA biofilms and reduced the production of exopolysaccharide, polysaccharide intercellular adhesin, and extracellular DNA and showed synergistic biofilm inhibition in combination with β-lactams. Transcriptome analysis revealed profound downregulation in the expression of genes involved in two-component systems and S. aureus infection. Mechanistic studies indicate that carvacrol inhibits the expression of staphylococcal accessory regulator sarA and interferes with SarA- mecA promoter binding that decreases mecA -mediated β-lactam resistance. Consistently, the in vivo experiment also supported that carvacrol restored MRSA sensitivity to β-lactam antibiotic treatments in both murine models of bacteremia and biofilm-associated infection. Our results indicated that carvacrol has a potential role as a combinatorial partner with β-lactam antibiotics to address MRSA infections.