Benmamoun, ZacharyChandar, PremJankolovits, JoeDucker, William A.2025-12-192025-12-192024-03-292373-9878https://hdl.handle.net/10919/140529Polycationic polymers are widely studied antiseptics, and their efficacy is usually quantified by the solution concentration required to kill a fraction of a population of cells (e.g., by Minimum Bactericidal Concentration (MBC)). Here we describe how the response to a polycationic antimicrobial varies greatly among members of even a monoclonal population of bacteria bathed in a single common antimicrobial concentration. We use fluorescence microscopy to measure the adsorption of a labeled cationic polymer, polydiallyldimethylammmonium chloride (PDADMAC, M-w approximate to 4 x 10(5) g mol(-1)) and the time course of cell response via a cell permeability indicator for each member of an ensemble of either Escherichia coli, Staphylococcus aureus, or Pseudomonas aeruginosa cells. This is a departure from traditional methods of evaluating synthetic antimicrobials, which typically measure the overall response of a collection of cells at a particular time and therefore do not assess the diversity within a population. Cells typically die after they reach a threshold adsorption of PDADMAC, but not always. There is a substantial time lag of about 5-10 min between adsorption and death, and the time to die of an individual cell is well correlated with the rate of adsorption. The amount adsorbed and the time-to-die differ among species but follow a trend of more adsorption on more negatively charged species, as expected for a cationic polymer. The study of individual cells via time-lapse microscopy reveals additional details that are lost when measuring ensemble properties at a particular time.application/pdfenCreative Commons Attribution 4.0 Internationalcationic polymeradsorptionbacteriaantimicrobialPDADMACE. coliArticle - Refereedhttps://doi.org/10.1021/acsbiomaterials.4c0026310538551901