Abstract 1745 Investigating the activity and mechanism of action of DesHDAP2 truncations

There is an urgency for alternative treatments to conventional antibiotics due to increasing rates of antibiotic resistance in bacteria. A strong alternative are antimicrobial peptides (AMPs) as it is less likely that bacteria will become resistant to AMPs due to their more generalized targets in the cell. Our lab developed novel histone-derived AMPs (HDAPs), including the DesHDAP2 peptide, which has been shown to have some antimicrobial activity in previous research. By gradually truncating this 21-residue-long peptide from the N or C terminus and looking at its activity, we strive to assess the minimal active length of DesHDAP2. To this end, we tested the activity of 10 different truncations and compared them to full-length DesHDAP2 against E. coli and B. subtilis using radial diffusion and microbroth dilution assays. The highest activity was seen in truncations with amino acids 1-18 and 2-20, implying that the region of DesHDAP2 that is needed to fully function contains amino acids 2-18. Since higher activity was observed against B. subtilis, ongoing work is evaluating the activity of DesHDAP2 against other gram-positive strains and considering the mechanism of action for DesHDAP2-related peptides in propidium iodide membrane permeabilization assays. This work is supported by award 1R15AI169210 from the NIH/NIAID.