Alternatives to antibiotics: biotechnological approach to deliver recombinant bioactive proteins

Abstract Text: With the growing concern of the bacterial resistance to conventional antibiotics, time has come for us to search for alternative to antibiotics in animal production. In the past six years, our laboratory has been working on establishing a platform for cost effective production of recombinant bioactive peptides, and evaluation of their efficiency both in vitro and in vivo. Candidate peptides may be derived from a variety of sources (e.g., milk, mammalian cell), and may be selected based on direct anti-microbial role such as Protegrin-1 (PG-1), or stimulation of gut health and development (e.g., epidermal growth factor; EGF); Using Lactococcus lactis and yeast as hosts, our laboratory has previously produced recombinant porcine EGF, animal trials demonstrated that it enhances the growth performance and intestine development of early weaned pig fed with antibiotic free diet.  PG-1 is a porcine cathelicidin antimicrobial peptide that can exert its activity against a broad range of microorganisms, including bacteria that are resistant to convertional antibiotics. In addition, as the peptide is an integral part of the innate immune system, it may have other functions such as immuno- modulating effects, similar to its human cathelicidin counterpart. More recently, we have generated codon-optimized proform PG-1, mature PG-1 for expression in Pichia pastoris. We also investigated the potential inflammatory modulating and protective role of PG-1 in a dextran sulfate sodium (DSS)-induced colitis murine model. Protegrin treatment prevented colitis-induced body weight loss and improved disease activity index (DIA) scoring (P < 0.05) compared to the untreated DSS-control mice. Histological analyses indicate reduced mucosal erosion and sub-mucosa inflammation in protegrin-treated groups. In addition, relative expression of inflammatory factors (COX2 and TNFa) was significantly reduced in protegrin treatment groups compared to the colitis group (P < 0.05). Overall, oral administration of protegrin was demonstrated to be protective against colitis induction in the animal model.  Resulting data establishes the potential application of protegrins to modulate intestinal health in vivo. These examples illustrate the potential for cost-effective production and application of recombinant bioactive proteins as alternatives to antibiotics in swine production.

Keywords: antimicrobial peptide, biotechnology, antibiotic resistance, immunoprotection, tissue repair