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Epinecidin-1 antimicrobial activity: In vitro membrane lysis and In vivo efficacy against Helicobacter pylori infection in a mouse model.

Abstract：

:Helicobacter pylori (H. pylori) infection is highly prevalent, and has a strong association with various gastric diseases, including gastritis, digestive ulcers, and cancer. H. pylori strains with resistance to existing antibiotics have emerged in the past two decades. Currently, treatment of H. pylori infection (involving the use of proton pump inhibitors, followed by triple therapy with broad-spectrum antibiotics) is suboptimal, with high failure rates. As such, there is a clear need for new approaches against H. pylori. Here, we report that Epinecidin-1 (Epi-1) shows effective bactericidal activity against H. Pylori in vitro, and modulates H. Pylori-induced host immune responses in a mouse model. Epi-1 exhibited a low minimum inhibitory concentration (MIC) against antibiotic-sensitive and clinical antibiotic-resistant strains. Moreover, Epi-1 treatment caused 1-N-phenylnaphthylamine (NPN)-fluorescent probe uptake, suggesting it induced membrane lysis; transmission electron micrographs revealed that membranes were destabilized by the generation of saddle-splay membrane curvature. Oral administration of Epi-1 (quaque die dose) in a mouse infection model had strong efficacy (p < 0.00152) against H. pylori, as compared with conventional proton pump inhibitor (PPI)-triple therapeutic antibiotics. Epi-1 inhibited infection through in vivo depletion of CD4+-FOXP3+ T Regulatory and Th17 subset populations, and aided in clearance of persistent H. pylori colonization. Flow cytometry and gene expression analysis of mouse splenic and gastric tissue indicated that Epi-1 inhibits IL-10, and thereby affects FOXP3 expression levels and reduces pro-inflammatory cytokine responses. Crucially, high doses of Epi-1 did not exert toxic effects in oral, dermal, and eye irritation models. Collectively, our results suggest that Epi-1 may be a promising, effective, and safe monotherapeutic agent for the treatment of multi-drug resistant H. pylori infection.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Narayana JL,Huang HN,Wu CJ,Chen JY

doi

10.1016/j.biomaterials.2015.05.014

subject

Has Abstract

pub_date

2015-08-01 00:00:00

pages

41-51

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(15)00464-0

journal_volume

pub_type

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Epinecidin-1 antimicrobial activity: In vitro membrane lysis and In vivo efficacy against Helicobacter pylori infection in a mouse model.