Modern large-scale agricultural practices which incorporate high density farming with sub-therapeutic antibiotic dosing are a major contributor to the rise of antibiotic resistant bacterial infections. A leading foodborne pathogen, Salmonella, is present on as much as 20% of all packaged chicken products with 15% of those isolates found to be resistant to 4 or more antibiotics by the Centers for Disease Control. Alternatives to antibiotics, such as antimicrobial peptides (AMP) offer higher levels of specificity and activity towards targets of interest compared to traditional antibiotics. To this end, Microcin J25, a 21 amino acid AMP with a highly stable threaded lasso structure is being studied with single-site saturation mutagenesis and deep sequencing to evaluate mutations contributing to the specificity and activity against multiple Salmonella and Escherichia coli strains. Utilizing this information, variants of Microcin J25 will be generated which reduce off-target activity against non-Salmonella bacteria while maintaining efficacy against pathogenic targets. These in vitro specificity improvements are likely to improve in vivo treatment efficacy by reducing clearance of commensal bacteria in the gastrointestinal tract of host animals.

Saturation mutagenesis panning libraries enable activity and specificity modulation of Microcin J25

253rd National Meeting (2017)

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