Development of peptides for use as antimicrobial agents

Pathogenic bacteria are evolving resistance to conventional therapeutics at a rate which threatens our ability to reliably treat infections, necessitating the discovery of new therapeutics. Here, I employ the development of novel peptides that can be used to combat antimicrobial resistance. In Chapter 2, I employ a permutation of two known antimicrobial peptides (AMPs), Indolicidin and UyCT3, and through sequential generations of evolution, develop a peptide that can inhibit bacterial growth better than the wild type AMP. These AMPs are tested on clinically derived strains to help translate the clinical relevance of these findings. In Chapter 3, I use an orientated peptide array library (OPAL) to assist in the discovery of peptide β-lactamase inhibitors against the β-lactamase TEM-1. Candidates' activities were assessed for inhibition against TEM-1. These results show the significance of our findings and the robustness of the techniques that can be used for the discovery of peptide antimicrobials.