Antimicrobial Peptides: A Solution for Antibiotic Resistance?

Antibiotic resistance is an ever-growing global health problem. Over the years, bacteria managed to develop strategies to resist antibiotics, urging us to search for alternative options. Antimicrobial peptides (AMPs) are one of the candidates that hold promise for combatting the resistant bacteria. AMPs are one the components of the innate immunity in multicellular organisms, including humans, and their mechanism of action is thought to be insusceptible to genetically-developed resistance. AMPs success in medicine, however, relies on new designs that are highly toxic for bacteria, yet, selective enough not to harm human cells. The overall goal of this project is to quantifying the activity of AMPs at the single-cell level. Such quantitative data reveals information on the heterogeneity and the population dynamics of the AMPs' action. In this project, we first aim at (1) utilizing a novel single-cell imaging platform, ?mother machine?, for precise monitoring of AMPs? effect on live bacterial cells. Mother machine is a PDMS based microfluidics device in which cells grow in a tightly-controlled microenvironment where we can administer drugs. The device design allows high-throughput video microscopy on individual cells. Next aim is (2) deep analysis of the single-cell data to obtain information on the dynamics of cell death and heterogeneity in bacterial populations. Since resistance (or persistence) of even a small fraction of cells to antibiotics can fail a treatment, this is important to quantify responses of bacteria at the single-cell level. The final aim is this proposal is (3) investigating the relationship between activity and physical properties of AMPs. To this end, we plan to test different AMPs with various physiochemical parameters and extract any correlation between these parameters and AMPs' activity. Broadly, the outcome of this project uncovers AMPs' activity on a large population of bacteria at the single-cell level. The modern imaging and single-cell cultivation approach of this work will also open up possibilities for further investigations on the cellular and molecular mechanisms of AMPs' activity.