Bacteriocin IIa antimicrobial proteins (AMPs) are a protein family characterized by small size (roughly 30-50 amino acids), simple protein structure, and strain-specific targeting of the mannose phosphotransferase systems (manPTSs) of various gram-positive bacteria. Given their high specificity, bacteriocin IIa AMPs are one potential alternative to broad-spectrum antibiotics for treating various bacterial infections, with vancomycin-resistant Enterococci (VRE) garnering particular interest. However, it is poorly understood how varying bacteriocin IIa protein sequence affects AMP potency and selectivity; thus, it is unclear how to best engineer these AMPs as therapeutics. Towards this goal, we are experimentally evaluating the Enterococcal inhibitory activity of 230 naturally occurring and rationally designed bacteriocin IIa AMPs and 900 random multi-mutants of six previously characterized bacteriocin IIa AMPs. We screened these two pools of AMPs expressed in L. lactis against six strains of Enterococcus and identified functional clones using high-throughput sequencing. We identified a total of 66 unique AMPs which displayed antimicrobial activity and are individually producing these AMPs to identify selective, potent molecules through quantification of the minimum inhibitory concentration across several Enterococcus strains. The activity data will then be mapped to the AMP and manPTS sequences to identify protein interactions which determine AMP selectivity and activity. The emerging data linking sequence and multi-strain potency will identify sequence-function relationships for informing future bacteriocin IIa rational design.

Characterization of natural bacteriocin IIa antimicrobial proteins to map sequence-function relationships

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.