Abstract
The zoonotic enterohaemorrhagic Escherichia coli (EHEC) O157:H7 can disrupt intestinal epithelial barrier function and in turn leading to serious intestinal and systemic disease. PR39 could effectively inhibit the growth of Gram-negative bacteria, but there is little knowledge of its effects on intestinal barrier function and the microbiota in E. coli-challenged mice. In this study, an intestinal disease caused by EHEC O157:H7 was established, to analyze the effect of PR39 on EHEC O157:H7 induced intestinal epithelial barrier injury and disorder. Interestingly, PR39 attenuated EHEC O157:H7-induced systemic symptoms and significantly decreased mortality and the degree of E. coli shedding in faeces. Furthermore, the infiltration index of macrophages and neutrophils in intestine of the PR39 treatment group were obviously attenuated, along with the level of apoptosis. PR39 treatment group had distinctly improved tight junction associated proteins’ expression after EHEC O157:H7 caused injury. Additionally, the sequencing analysis of cecum microbiota showed that PR39 altered the abnormal increase in Bacteroides caused by EHEC O157:H7 and promoted the growth of probiotics such as Lactobacillus. In conclusion, cathelicidin-derived PR39 could effectively improve EHEC O157:H7-induced epithelial barrier injury, and dysfunction of immune and microbiota homeostasis in the intestinal tract, indicating that PR39 could be an excellent potential drug for zoonotic EHEC O157:H7-related intestinal disease.
Highlights
Enterohaemorrhagic Escherichia coli (EHEC), as pathogenic subgroup of Shiga toxin-producing E. coli (STEC)[1], can produce Shiga toxins 1 and/ or 2 (Stx[1] and Stx2) and usually have an adhesion gene
Clinical features caused by EHEC O157:H7 were macroscopic soft shit, listless, no appetite and no desire to to move were observed in EHEC O157:H7 induced group compared with other three groups
We found that the inoculation of E. coli O157:H7 significantly lowered the weight of mice, as well as survival rate, and the administration of PR39 significantly improved these trends ((Supplemental Fig. S1)
Summary
Enterohaemorrhagic Escherichia coli (EHEC), as pathogenic subgroup of Shiga toxin-producing E. coli (STEC)[1], can produce Shiga toxins 1 and/ or 2 (Stx[1] and Stx2) and usually have an adhesion gene (eae). E. coli O157:H7 is the most common serotype of EHEC2, it is one of the most prevalent serotypes causing diarrhoea in humans, adhering tightly to the intestinal mucosa to form attaching and effacing lesions. The Shiga toxin (Stx) secreted by E. coli O157:H7 can pass through the intestinal epithelium and induce systemic damage[3], generating inflammatory responses and causing apoptosis of epithelial cells. The effects of the antimicrobial peptide PR39 on EHEC O157:H7-caused systemic disorder and symptoms remain unreported, as does the function of PR39 in recovery from dysbiosis. This study explored the effects of PR39 on the inflammatory level, gastrointestinal epithelial function, and intestinal microbiota, using a mouse model of EHEC O157:H7 infection
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