Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, Korea.
Int J Mol Sci. 2021 Mar 9;22(5):2752. doi: 10.3390/ijms22052752.
Methicillin-resistant (MRSA) is a major nosocomial pathogen worldwide and has acquired multiple resistance to a wide range of antibiotics. Hence, there is a pressing need to explore novel strategies to overcome the increase in antimicrobial resistance. The present study aims to investigate the efficacy and mechanism of plant-derived antimicrobials, trans-cinnamaldehyde (TCA) in decreasing MRSA's resistance to eight conventional antibiotics. A checkerboard dilution test and time-kill curve assay are used to determine the synergistic effects of TCA combined with the antibiotics. The results indicated that TCA increased the antibacterial activity of the antibiotics by 2-16-fold. To study the mechanism of the synergism, we analyzed the transcription gene and the penicillin-binding protein 2a level of MRSA treated with TCA by quantitative RT-PCR or Western blot assay. The gene transcription and the protein level were significantly inhibited. Additionally, it was verified that TCA can significantly inhibit the biofilm, which is highly resistant to antibiotics. The expression of the biofilm regulatory gene of MRSA after TCA treatment was also significantly downregulated. These findings suggest that TCA maybe is an exceptionally potent modulator of antibiotics.
耐甲氧西林金黄色葡萄球菌(MRSA)是全球主要的医院病原体,对多种抗生素产生了多重耐药性。因此,迫切需要探索新的策略来克服抗菌药物耐药性的增加。本研究旨在探讨植物源抗菌剂反式肉桂醛(TCA)降低 MRSA 对八种常规抗生素耐药性的疗效和机制。采用棋盘稀释试验和时间杀伤曲线试验来确定 TCA 与抗生素联合使用的协同作用。结果表明,TCA 使抗生素的抗菌活性提高了 2-16 倍。为了研究协同作用的机制,我们通过定量 RT-PCR 或 Western blot 分析了 TCA 处理后 MRSA 的转录基因和青霉素结合蛋白 2a 水平。基因转录和蛋白水平均受到明显抑制。此外,还验证了 TCA 可以显著抑制高度耐抗生素的生物膜。TCA 处理后,MRSA 的生物膜调控基因的表达也明显下调。这些发现表明,TCA 可能是一种非常有效的抗生素调节剂。