Abstract
Concerns over the increasing emergence of antibiotic-resistant pathogenic microorganisms due to the overuse of antibiotics and the lack of effective antibiotics for livestock have prompted efforts to develop alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) with a broad-spectrum activity and rapid killing, along with little opportunity for the development of resistance, represent one of the promising novel alternatives. Their high production cost and cytotoxicity, however, limit the use of AMPs as effective antibiotic agents to livestock. To overcome these problems, we developed potent antimicrobial Escherichia coli displaying multimeric AMPs on the cell surface so that the AMP multimers can be converted into active AMP monomers by the pepsin in the stomach of livestock. Buf IIIb, a strong AMP without cytotoxicity, was expressed on the surface of E. coli as Lpp-OmpA-fused tandem multimers with a pepsin substrate residue, leucine, at the C-terminus of each monomer. The AMP multimers were successfully converted into active AMPs upon pepsin cleavage, and the liberated Buf IIIb-L monomers inhibited the growth of two major oral infectious pathogens of livestock, Salmonella enteritidis and Listeria monocytogenes. Live antimicrobial microorganisms developed in this study may represent the most effective means of providing potent AMPs to livestock, and have a great impact on controlling over pathogenic microorganisms in the livestock production.
Highlights
Modern livestock production systems have continually used antibiotics and antimicrobial compounds to either prevent and treat infectious diseases or improve weight gain and feed utilization in animals
Many countries have banned the administration of conventional antibiotics, as feed additives to livestock [6,7]
Earlier experiments disclosed that Buf IIIb exhibits potent antimicrobial activity via targeting intracellular components, such as DNA in microorganisms, and does not cause damage to mammalian cells at the same time, resulting in a 7-fold improvement in the therapeutic index, compared to its parent antimicrobial peptide, buforin IIb [13]
Summary
Modern livestock production systems have continually used antibiotics and antimicrobial compounds to either prevent and treat infectious diseases or improve weight gain and feed utilization in animals. The indiscriminate non-therapeutic use of antibiotics in the livestock production has a negative impact on livestock and on public health and food safety, as it promotes the rapid development of multidrug-resistant bacteria that do not respond to current antibiotics, further endangering human lives [2,3,4,5]. These antibiotic-resistant bacterial strains and associated genes have the potential to impart their resistance traits to disease-causing bacteria. The rapid increase in the number of antibiotic-resistant pathogenic microorganisms due to antibiotic overuse as well as the limited number and low availability of effective antibiotics for livestock has led to numerous researchers focus on the development of alternatives to conventional antibiotics [8,9,10]
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