
艾迪生和EDTA與多粘菌素E的三聯組合可以顯著增強對沙門氏菌的抗菌活性,主要通過增加細胞膜損害、積累毒性化合物和抑制MCR-1等機制發揮協同作用。


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Discovering new strategies to combat the multi-drug resistance bacteria constitutes a major medical challenge of our time. Previously, artesunate (AS) has been reported to exert antibacterial enhancement activity in combination with β-lactam antibiotics, via inhibition of the efflux pump AcrB. However, combination of AS and colistin (COL) revealed weak synergistic effect against a limited number of strains, and few studies have further explored its possible mechanism of synergistic action. In this paper, we found that AS and EDTA could strikingly enhance the antibacterial effects of COL against mcr - 1 − and mcr - 1 + Salmonella strains either in vitro or in vivo , when used in triple combination. The excellent bacteriostatic effect was primarily related to the increased cell membrane damage, accumulation of toxic compounds and inhibition of MCR-1. The potential binding sites of AS to MCR-1 (THR283, SER284, and TYR287) were critical for its inhibition of MCR-1 activity. Additionally, we also demonstrated that the CheA of chemosensory system and virulence-related protein SpvD were critical for the bacteriostatic synergistic effects of the triple combination. Selectively targeting CheA, SpvD or MCR using the natural compound artesunate could be further investigated as an attractive strategy for treatment of Salmonella infection. Collectively, our work opens up avenues towards the potentiation of colistin and revealed an alternative drug combination strategy to overcome COL resistant bacterial infections.

### Competing Interest Statement

The authors have declared no competing interest.

Artesunate, EDTA and colistin work synergistically against MCR-negative and -positive colistin-resistant Salmonella

艾迪生-edta和多粘菌素e對mcr陰性和陽性多藥耐藥沙門氏菌具有協同作用


艾迪生、EDTA和多粘菌素E對mcr陰性和陽性多藥耐藥沙門氏菌具有協同作用
