Population Dynamics of Antimicrobial Peptide's Activity is Governed by their Retention in Dead Bacterial Cells

Abstract

Antimicrobial peptides (AMPs) are broad spectrum antibiotics that utilize electrostatics to selectively target bacteria. Like every antibiotic, AMPs need a minimum concentration (known as MIC) to effectively inhibit growth of a bacterial population. Despite our molecular knowledge on AMPs, we still lack a comprehensive understanding of the AMP's dynamics at the cellular and the population level. In this talk, I present our recent findings that MIC of AMPs is strongly dependent on the cell density, even in dilute cultures where there is no direct cell-to-cell interactions. This suggests that individual cells may adsorb a large number of AMPs that considerably reduces their concentration in the solution. To further investigate this, we used a live single-cell imaging platform to track fluorescently tagged AMPs and the time evolution of their translocation into bacteria. Our single-cell analysis show that bacteria not only adsorb a large fraction of AMPs from the culture, but dead cells also retain them almost permanently which sequesters AMPs availability for attacking more cells.