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Repurposing Ellipticine Hydrochloride to Combat Colistin-Resistant Extraintestinal Pathogenic E. coli (ExPEC)

文献类型： 外文期刊

作者： Lu, Hao 1 ; Liu, Manli 5 ; Lu, Wenjia 1 ; Wang, Chenchen 1 ; Wang, Gaoyan 1 ; Dong, Wenqi 1 ; Wang, Xiangru 1 ; Chen, Hua 1 ;

作者机构： 1.Huazhong Agr Univ, Coll Vet Med, State Key Lab Agr Microbiol, Wuhan, Peoples R China

2.Cooperat Innovat Ctr Sustainable Pig Prod, Key Lab Prevent Vet Med Hubei Prov, Wuhan, Peoples R China

3.Minist Agr Peoples Republ China, Key Lab Dev Vet Diagnost Prod, Wuhan, Peoples R China

4.Minist Sci & Technol Peoples Republ China, Int Res Ctr Anim Dis, Wuhan, Peoples R China

5.Hubei Acad Agr Sci, Hubei Biopesticide Engn Res Ctr, Wuhan, Peoples R China

关键词： mcr-1; colistin; ellipticine hydrochloride; ExPEC; multidrug-resistant

期刊名称：FRONTIERS IN MICROBIOLOGY （ 影响因子：5.64； 五年影响因子：6.32 ）

ISSN： 1664-302X

年卷期： 2020 年 11 卷

页码：

收录情况： SCI

摘要： Extraintestinal pathogenic Escherichia coli (ExPEC) strains are the cause of a majority of human extraintestinal infections globally, resulting in enormous direct economic and medical costs. The plasmid-mediated, colistin-resistant gene mcr-1 has broken through the ultimate defense line against MDR Gram-negative pathogens. There is an urgent need to discover the new compound intended for colistin-resistant E. coli. In this study, antibacterial targets of ellipticine hydrochloride (EH) were confirmed by localized surface plasmon resonance (LSPR) and decatenation assay. The LSPR analysis exhibited good binding between EH and E. coli topoisomerase IV. In this study, a synergistic effect is obvious in the combination of EH and colistin, to which eight of ten strains showed synergy, while two isolates (20%) showed no difference. The bacteria enumeration analysis of EH treatment group suggested that the decreased bacterial titer can be observed in various tissues of infected mice. EH treatment significantly decreased the levels of a variety of pro-inflammatory factors, such as TNF-alpha and IL-6. Moreover, other related lesions, such as inflammatory cell infiltration, alveolar interstitial congestion, and edema were observed to be relieved to different extents. This study reveals the anti-E. coli potential activities and molecular mechanism of EH and the therapeutical effectiveness of EH application to animals. It provides us with a new option for fighting against multidrug-resistant ExPEC infections in the future.

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