title: Understanding the dark and light-enhanced bactericidal action of cationic conjugated polyelectrolytes and oligomers.
abstract: A multiscale investigation was carried out to study the dark and light-enhanced bactericidal mechanisms of poly(phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPEs) and oligo-phenylene ethynylenes (OPEs). On the morphological scale, Gram-negative E. coli cells exposed to CPE and OPE compounds in the dark show damage to the cell envelope, plasma membrane, and in some cases the cytoplasm, while with UV-irradiation, E. coli sustained catastrophic damages to both the cell envelope and cytoplasm. In contrast, the Gram-positive S. epi bacteria appeared intact when exposed to CPE and OPE compounds in the dark but showed damages to the cell envelope with UV-irradiation. To better understand the molecular basis of CPE- and OPE-induced morphological changes and damages to bacteria, we investigated the effect of these compounds on model bacterial plasma membrane and bacterial proteins and plasmid DNA. Measurements of dark membrane perturbation activity of the CPEs and OPEs using model lipid membranes support a carpet or detergent-like mechanism by which the antimicrobial compounds induce membrane collapse and phase transitions. Under UV-irradiation, E. coli bacteria exposed to CPEs and OPEs showed covalent modifications and damages to both cellular protein and plasmid DNA, likely through oxidative pathways mediated by singlet oxygen and subsequent reactive oxygen species sensitized by the CPE and OPE compounds. Our finding thus show that the antimicrobial polymers and oligomers exert toxicity toward Gram-negative bacteria by disrupting the morphology and structures of cell envelope and cytoplasm, including cellular components such as proteins and DNA, while exert toxicity toward Gram-positive bacteria by binding to and disrupting just the cell wall.
authors.affiliation: Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, New Mexico 87131-1341, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Jett
authors.forename: John
authors.initials: J
authors.lastname: Crum
authors.forename: Kirk S
authors.initials: KS
authors.lastname: Schanze
authors.forename: Eva Y
authors.initials: EY
authors.lastname: Chi
authors.forename: David G
authors.initials: DG
authors.lastname: Whitten
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects* / Q000528:radiation effects; D002473:Cell Wall / Q000187:drug effects* / Q000528:radiation effects; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D004987:Ethers / Q000737:chemistry*; D008051:Lipid Bilayers / Q000528:radiation effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010957:Plasmids / Q000037:antagonists & inhibitors / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis / Q000494:pharmacology*; D000071228:Polyelectrolytes; D058105:Polymerization; D026082:Singlet Oxygen / Q000737:chemistry; D013045:Species Specificity; D013212:Staphylococcus epidermidis / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000480:Alkynes; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004987:Ethers; D008051:Lipid Bilayers; D011073:Polyamines; D000071228:Polyelectrolytes; D026082:Singlet Oxygen; C436384:phenyleneethynylene