Towards Engineered Probiotics to Deliver Narrow-Spectrum Antimicrobial Peptides Against Drug-Resistant Enteric Bacteria

Worldwide medical complications related to multi-drug resistant Enterobacteriaceae are a major issue in modern healthcare.

Working towards the development of antibiotic alternatives, we utilize the ability to heterologously produce the antimicrobial peptides microcin H47 (MccH47) and I47 (MccI47) in order to inhibit growth of drug-resistant Enterobacteriaceae in static plate assays. Moreover, using a Maltose Binding Protein (MBP)-microcin fusion protein system we are able, for the first time, to purify H47 near homogeneity and analyze in liquid minimum inhibitory concentration (MIC) assays. Our data reveal different, but overlapping, spectrums for both microcins with high specificity of H47 for candidate members of E. coli, Shigella spp., Salmonella spp. and Proteus mirabilis, including multi-drug resistant isolates. Previously uncharacterized I47 observes high antimicrobial activity against Klebsiella pneumoniae.

Engineering probiotic strains like E. coli Nissle 1917 with the ability to overproduce these antimicrobial compounds provides a novel strategy for the treatment of antibiotic resistant pathogenic infections.