Abstract
The bacteriocin microcin J25 (MccJ25) inhibits the growth of Gram-negative pathogens including Salmonella and Shigella species, and Escherichia coli. This 21-amino acid peptide has remarkable stability to heat and extreme pH values and resistance to many proteases, thanks to a characteristic lasso structure. In this study, we used the dynamic simulator TIM-1 as gastro-intestinal tract model to evaluate the stability and antibacterial activity of MccJ25 during passage through the proximal portion of the human gastrointestinal tract. MccJ25 concentration was measured in the different simulator sections by HPLC, and inhibition of Salmonella enterica serotype Enteritidis was evaluated using qualitative and quantitative assays. LC-MS/MS analysis and subsequent molecular networking analysis on the Global Natural Product Social Molecular Networking platform (GNPS) and analysis of the peptide degradation in the presence of proteolytic enzymes mimicking the gastro-intestinal conditions permitted to delineate the fate of MccJ25 through identification of the main degradation products. MccJ25 was relatively stable under gastric conditions, but degraded rapidly in the compartment mimicking the duodenum, notably in the presence of pancreatin. Among pancreatin components, elastase I appeared primarily responsible for MccJ25 breakdown, while α-chymotrypsin was less efficient.
Highlights
Antibiotics have been used for nearly a century in human and veterinary medicine and for therapeutic or growth-promoting purposes in livestock production (Gustafson and Bowen, 1997; Gyles, 2008)
We examined the potential of microcin J25 (MccJ25), a well-studied bacteriocin produced by the Gramnegative species Escherichia coli and of high interest as a potential alternative to conventional antibiotics, because of its potent inhibitory activity against pathogens belonging to the genera Escherichia, Salmonella, and Shigella (Salomon and Farías, 1992; Sable et al, 2000; Rintoul et al, 2001; Vincent and Morero, 2009)
The stability and antibacterial activity of MccJ25 were first evaluated using a dynamic simulator of the upper GI tract (TIM1 system)
Summary
Antibiotics have been used for nearly a century in human and veterinary medicine and for therapeutic or growth-promoting purposes in livestock production (Gustafson and Bowen, 1997; Gyles, 2008). They remain the most widely used chemicals for treating infections. Overuse of antibiotics with structural features similar to those used in human medicine led to the emergence of pathogens with resistance to at least one antibiotic used to treat infections (Reardon, 2014) This worrying development led the European Union to declare a total ban on antibiotics as growth promoters in animal. Very few bacteriocins have been approved by regulatory agencies for use in food, medical or veterinary products, despite the increasing urgency of the demand for such compounds
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