Clavanin A improves outcome of complications from different bacterial infections.

The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.

Expression of metalloproteinases and interleukins on anastomoses in septic rats.

BACKGROUND: Anastomotic dehiscence is the most severe complication of colorectal surgery and its incidence increases in the presence of infection. It has been reported that immune factors or the activity of matrix metalloproteinases (MMP) may mediate the loss of anastomotic strength in the first postoperative days. In this study, we investigated the effects of abdominal sepsis on the MMP and interleukin (IL) gene expression in left colonic anastomoses in rats. MATERIALS AND METHODS: Forty rats were divided into two groups of 20 animals according to the presence (group S) or absence (group N) of sepsis induction by cecal ligation and perforation during left colonic anastomosis. Each group was divided into subgroups for euthanasia on the third (N3 and S3) or seventh (N7 and S7) postoperative day (POD). A colonic segment containing anastomosis was removed for analysis of the expression of MMP1a, MMP8, MMP13, IL1ß, IL6, IL10, TNFα, and IFNγ genes. RESULTS: The anastomoses with abdominal sepsis showed increased MMP1a gene expression and decreased MMP8 gene expression both on the third and seventh POD. There was no change in the expression of MMP13. There was an increase in the expression of IL10 only on the third POD and a negative modulation of IL1ß, IFNγ, and IL6 genes on both periods. The TNFα gene expression was negatively modulated on the third POD and became not modulated on the seventh POD. CONCLUSION: Abdominal sepsis induced a specific inflammatory pattern with increased MMP1a and IL10 gene expression and negative modulation of MMP8, IL1ß, IFNγ, and TNFα gene expression in left colonic anastomoses in rats.