Dark Antimicrobial Mechanisms of Cationic Phenylene Ethynylene Polymers and Oligomers against Escherichia coli

The interactions of poly(phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and oligo-phenylene ethynylenes (OPEs) with E. coli cells are investigated to gain insights into the differences in the dark killing mechanisms between CPEs and OPEs. A laboratory strain of E. coli with antibiotic resistance is included in this work to study the influence of antibiotic resistance on the antimicrobial activity of the CPEs and OPEs. In agreement with our previous findings, these compounds can efficiently perturb the bacterial cell wall and cytoplasmic membrane, resulting in bacterial cell death. Electron microscopy imaging and cytoplasmic membrane permeability assays reveal that the oligomeric OPEs penetrate the bacterial outer membrane and interact efficiently with the bacterial cytoplasmic membrane. In contrast, the polymeric CPEs cause serious damage to the cell surface. In addition, the minimum inhibitory concentration (MIC) and hemolytic concentration (HC) of the CPEs and OPEs are also measured to compare their antimicrobial activities against two different strains of E. coli with the compounds' toxicity levels against human red blood cells (RBC). MIC and HC measurements are in good agreement with our previous model membrane perturbation study, which reveals that the different membrane perturbation abilities of the CPEs and OPEs are in part responsible for their selectivity towards bacteria compared to mammalian cells. Our study gives insight to several structural features of the PPE-based CPEs and OPEs that modulate their antimicrobial properties and that these features can serve as a basis for further tuning their structures to optimize antimicrobial properties.