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

Frontiers in Microbiology
Hao LuChen Tan

Abstract

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 reliev...Continue Reading

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Citations

Apr 30, 2021·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Majid Taati MoghadamShahla Shahbazi

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Methods Mentioned

BETA
electrophoresis
Surface Plasmon Resonance
chip
chips
Assay

Software Mentioned

Trace Drawer
GraphPad Prism
Labsolutions LCMS
Open SPR

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