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

Frontiers in Microbiology

卷:11

Chen Tan¹  Manli Liu¹  Chenchen Wang²  Hao Lu²  Huanchun Chen²  Gaoyan Wang²  Xiangru Wang²  Wenqi Dong²  Wenjia Lu² 

[1] Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Sciences, Wuhan, China;

[2] International Research Center for Animal Disease, Ministry of Science and Technology of the People’s Republic of China, Wuhan, China;

[3] Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture of the People’s Republic of China, Wuhan, China;

[4] Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China;

[5] State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China;

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

DOI  :  10.3389/fmicb.2020.00806

来源: DOAJ

【 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-α 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.

【 授权许可】

Unknown