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

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 tightjunction protein ZO1 in duodenum and ileum epithelium after ETEC-challenge. Moreover, BMGlvA2 significantly downregulated 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.

G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion

“…ETEC has been demonstrated to induce cell death and decrease the expression of tight junction proteins in intestinal epithelial cells ( 29 – 31 ) and a mouse model ( 32 ). In this experiment, we also found that ETEC significantly decreased the expression of tight junction proteins.…”

The Antimicrobial Peptide Mastoparan X Protects Against Enterohemorrhagic Escherichia coli O157:H7 Infection, Inhibits Inflammation, and Enhances the Intestinal Epithelial Barrier

“…The TJ structure is composed of TJ proteins, such as ZO-1, occludin, and claudins, which are an important part of the intestinal epithelial barrier and play important roles in intestinal epithelial cells ( Huang et al, 2020 ). Lin et al (2019) investigated the effect of the antimicrobial peptide gloverin A2 (BMGlvA2) on ETEC-induced intestinal barrier disruption in mice and found that it clearly improved the expression of the TJ protein ZO-1 in the intestine after ETEC infection. Zhang et al (2019) found that the hybrid peptide LL-37-Tα1 (LTA) could increase the LPS-induced expression of ZO-1 and occludin in the jejunum of mice, thereby improving intestinal barrier function.…”

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“…ETEC has been demonstrated to induce cell death and decrease the expression of tight junction proteins in intestinal epithelial cells (29)(30)(31)) and a mouse model (32). In this experiment, we also found that ETEC significantly decreased the expression of tight junction proteins.…”