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

Xueqin Zhao,Yundi Wu,Jinqing Jiang,Hanna Fotina,Chunling Zhu,Xilong Wu,Huihui Zhang,Lei Wang,Xiaojing Xia,Yueyu Bai,Yimin Wang,Jianhe Hu,Shouping Zhang,Gaiping Zhang,Yanzhao Xu,Shijun Chen,Shanqin Liu

doi:10.3389/fmicb.2021.644887

Abstract

Escherichia coli can cause intestinal diseases in humans and livestock, destroy the intestinal barrier, exacerbate systemic inflammation, and seriously threaten human health and animal husbandry development. The aim of this study was to investigate whether the antimicrobial peptide mastoparan X (MPX) was effective against E. coli infection. BALB/c mice infected with E. coli by intraperitoneal injection, which represents a sepsis model. In this study, MPX exhibited no toxicity in IPEC-J2 cells and notably suppressed the levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and lactate dehydrogenase (LDH) released by E. coli. In addition, MPX improved the expression of ZO-1, occludin, and claudin and enhanced the wound healing of IPEC-J2 cells. The therapeutic effect of MPX was evaluated in a murine model, revealing that it protected mice from lethal E. coli infection. Furthermore, MPX increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum. SEM and TEM analyses showed that MPX effectively ameliorated the jejunum damage caused by E. coli and increased the number and length of microvilli. In addition, MPX decreased the expression of IL-2, IL-6, TNF-α, p-p38, and p-p65 in the jejunum and colon. Moreover, MPX increased the expression of ZO-1, occludin, and MUC2 in the jejunum and colon, improved the function of the intestinal barrier, and promoted the absorption of nutrients. This study suggests that MPX is an effective therapeutic agent for E. coli infection and other intestinal diseases, laying the foundation for the development of new drugs for bacterial infections.

Highlights

Escherichia coli is a facultative anaerobe that causes diarrhea, enteritis, host intestinal barrier damage, and intestinal microecological disorders, which have high mortality rates and result in substantial losses worldwide (Glombowsky et al, 2020)
Compared with the control treatment, the results showed that cell viability analyzed by the CCK-8 assay was not affected, but it might increase cellular metabolism when cells were supplemented with mastoparan X (MPX) (Figure 1A)
These results indicated that MPX maintained the cellular membrane integrity of IPEC-J2 cells

Summary

Introduction

Escherichia coli is a facultative anaerobe that causes diarrhea, enteritis, host intestinal barrier damage, and intestinal microecological disorders, which have high mortality rates and result in substantial losses worldwide (Glombowsky et al, 2020). Escherichia coli can induce urinary tract infections and meningitis in neonates (Chen et al, 2020). Antibiotics are currently effective in treating E. coli infections, diseases caused by E. coli have high degrees of sequelae (Ding et al, 2020). Antibiotics are the primary treatment for many pathogenic E. coli strains infection in animal production, leading to increased resistance to antibiotics, such as ampicillin, florfenicol, and gentamicin (Smith et al, 2016). There is a dire need to explore new antibiotic alternatives to resist E. coli infections

Objectives

Methods

Results

Discussion

Conclusion