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 towards 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 towards Gram-positive bacteria by binding to and disrupting just the cell wall.

Antimicrobial photodynamic activity and cytocompatibility of Au₂₅(Capt)₁₈ clusters photoexcited by blue LED light irradiation

“…26 In addition, ROS destroy the ligation moieties of nucleic acids, base and sugar groups, and subsequently suspend DNA replication. 27 Furthermore, generation of ROS leads to the modification of amino acid side chains of proteins, causing degradation. Damaged proteins subsequently affect 25 (capt) 18 cluster-mediated photodynamic effects intracellular pathways and disturb cellular metabolism.…”

“…Damaged proteins subsequently affect 25 (capt) 18 cluster-mediated photodynamic effects intracellular pathways and disturb cellular metabolism. 27 Ichinose-tsuno et al 28 reported that aPDT using toluidine blue O and red LED facilitated an inhibitory effect on plaque formation. Fontana et al 29 and O'Neill et al 30 showed that application of dye photosensitizers, including MB and toluidine blue O, under red light irradiation inhibited plaque formation and significantly increased bacterial cell death and destruction of biofilms in the oral cavity, suggesting that 1 O 2 could penetrate dental plaque and subsequently cause destruction through antimicrobial effects.…”

Antimicrobial Activity of Cationic Conjugated Polyelectrolytes and Oligomers against Saccharomyces cerevisiae Vegetative Cells and Ascospores

“…10−12 The cytoplasm of Gram-negative bacteria has been shown to be destroyed by the corrosive radicals. 10 Because of the general mechanism(s) by which CPEs and OPEs inactivate bacteria and viruses, we investigate in this study the utility of the compounds as antifungal agents. The antifungal activities of a set of antimicrobial CPEs and OPEs against the vegetative eukaryotic Saccharomyces cerevisiae (S. cerevisiae) cells and ascospores/asci were measured.…”

Exploring Novel Polymer Coatings for Antimicrobial Applications

“…Thus, the antibiotic efficiency of the polymers was significantly enhanced. Similar antibiotic activity was also observed by Wang et al 190 when comparing the antibiotic action of a library of PPE polyelectrolyte and oligomer derivatives.…”