Cui Kaiyu, Yang Weifeng, Liu Shuang, Li Dongying, Li Lu, Ren Xing, Sun Yanan, He Gaiying, Ma Shuhua, Zhang Jidan, Wei Qing, Wang Yi
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Nanchang Institute of Technology, Nanchang 330044, China.
Antibiotics (Basel). 2022 Dec 31;12(1):71. doi: 10.3390/antibiotics12010071.
Methicillin-resistant (MRSA) has posed a severe global health threat. In this study, we screened an antibiotic and non-antibiotic combination that provides a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA) could synergistically act with carbapenem antibiotics to eradicate MRSA-related infections. This synergy specifically targets MRSA and was also validated using 25 clinical MRSA strains using time-kill analysis. We speculated that the underlying mechanism was associated with the interaction of penicillin-binding proteins (PBPs). As a result, the synergistic efficiency of CDCA with carbapenems targeting PBP1 was better than that of β-lactams targeting PBPs. Moreover, we showed that CDCA did not affect the expression level of PBPs, but sensitized MRSA to carbapenems by disrupting the cell membrane. In our study, we have revealed a novel synergistic combination of antibiotics and non-antibiotics to combat potential bacterial infections.
耐甲氧西林金黄色葡萄球菌（MRSA）已对全球健康构成严重威胁。在本研究中，我们筛选了一种抗生素与非抗生素的组合，通过拓宽抗菌谱为解决这一问题提供了可行策略。我们发现鹅去氧胆酸（CDCA）可与碳青霉烯类抗生素协同作用以根除与MRSA相关的感染。这种协同作用特异性针对MRSA，并且还通过时间杀菌分析使用25株临床MRSA菌株进行了验证。我们推测其潜在机制与青霉素结合蛋白（PBPs）的相互作用有关。结果，CDCA与靶向PBP1的碳青霉烯类药物的协同效率优于靶向PBPs的β-内酰胺类药物。此外，我们表明CDCA不影响PBPs的表达水平，但通过破坏细胞膜使MRSA对碳青霉烯类药物敏感。在我们的研究中，我们揭示了一种新型的抗生素与非抗生素协同组合，以对抗潜在的细菌感染。
