Bombyx mori gloverin A2 alleviates enterotoxigenic Escherichia coli-induced inflammation and intestinal mucosa disruption

Antimicrob Resist Infect Control. 2019 Nov 26:8:189. doi: 10.1186/s13756-019-0651-y. eCollection 2019.

Abstract

Background: Enterotoxigenic Escherichia coli (ETEC) is one of the leading bacterial causes of intestinal inflammation and diarrhea. However, the ETEC is frequently resistant to common antibiotics. In this study, we explored the role of a novel antibacterial peptide Bombyx mori gloverin A2 (BMGlvA2) in alleviating ETEC-induced inflammation and intestinal epithelium disruption in mice.

Methods: An ETEC-challenged mice model was used, and the ETEC-challenged mice and non-challenged mice were treated by the BMGlvA2 at different doses.

Results: ETEC challenge not only elevated the concentrations of serum inflammatory cytokines such as the IL-6 and TNF-α (P < 0.01), but also elevated the concentrations of serum creatinine and urea (P < 0.05). However, BMGlvA2 attenuated the inflammatory responses by decreasing the serum inflammatory cytokines and improving the metabolisms in ETEC-challenged mice, and alleviated the ETEC-induced tissue damage in spleen. Moreover, BMGlvA2 treatment significantly elevated the duodenum villus height and decreased the crypt depth in the duodenum and ileum in ETEC-challenged mice (P < 0.05). Interestingly, BMGlvA2 improved the distribution and abundance of tight-junction protein ZO1 in duodenum and ileum epithelium after ETEC-challenge. Moreover, BMGlvA2 significantly down-regulated the expression levels of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and the apoptosis-related genes (Caspase 8 and Caspase 9) in jejunal mucosa (P < 0.05) in the TETC-challenged mice. Importantly, BMGlvA2 significantly elevated the expression levels of critical genes related to mucosal barrier functions such as the mucins (MUC1 and MUC2) and glucose transporter (GLUT2) in the intestinal mucosa (P < 0.05).

Conclusion: Our results suggested a novel function of the conventional antibacterial peptides, and the anti-bacterial and anti-inflammatory properties of BMGlvA2 may allow it a potential substitute for conventionally used antibiotics or drugs.

Keywords: BMGlvA2; E. coli K88; Inflammation; Intestinal mucosa; Mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Cytokines / blood
  • Disease Models, Animal
  • Enterotoxigenic Escherichia coli / drug effects*
  • Escherichia coli Infections / prevention & control*
  • Inflammation / microbiology
  • Inflammation / prevention & control*
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred ICR

Substances

  • Anti-Bacterial Agents
  • Cytokines
  • Intercellular Signaling Peptides and Proteins
  • gloverin