Direct Visualization of Bactericidal Action of Cationic Conjugated Polyelectrolytes and Oligomers

Abstract

The bactericidal mechanisms of poly(phenylene ethynylene) (PPE)-based cationic conjugated polyelectrolytes (CPE) and oligo-phenylene ethynylenes (OPE) were investigated using electron/optical microscopy and small-angle X-ray scattering (SAXS). The ultrastructural analysis shows that polymeric PPE-Th can significantly remodel the bacterial outer membrane and/or the peptidoglycan layer, followed by the possible collapse of the bacterial cytoplasm membrane. In contrast, oligomeric end-only OPE (EO-OPE) possesses potent bacteriolysis activity, which efficiently disintegrates the bacterial cytoplasm membrane and induces the release of bacterial cell content. Using single giant vesicles and SAXS, we demonstrated that the membrane perturbation mechanism of EO-OPE against model bacterial membranes results from a 3D membrane phase transition or perturbation.

Understanding the Dark and Light-Enhanced Bactericidal Action of Cationic Conjugated Polyelectrolytes and Oligomers

“…As reported previously in a letter, 9 due to the large differences in molecular weights, the polymeric CPEs and oligomeric OPEs exert dark antimicrobial activity against the Gram-negative E. coli bacteria via different mechanisms. For example, the large polymeric PPE-Th (Scheme 1) primarily damages the bacterial cell surface.…”

“…9, 17, 40 However, PPE-Th is not expected to penetrate through the bacterial envelop and get into the cytoplasm due to its high molecular weight. 9 In contrast, EO-OPE-1(C3) with its needlelike structure may easily penetrate through the outer membrane and the thin peptidoglycan layer in the bacteria without causing serious structural damages. Subsequently, it can reach, perturb and even penetrate the bacterial cytoplasmic membrane, leading to cell lysis.…”

“…9, 27 The UV-light irradiation experiments were carried out in a photoreactor (LZC-ORG, Luzchem Research Inc., Ottawa, Canada) at room temperature. Different illumination sources were used according to the different light-absorbing properties of the CPEs and OPEs.…”

“…For example, the small oligomeric EO-OPE-1(C3) (Scheme 1) can disrupt model bacterial membranes and induce a phase transition from a lamellar to a hexagonal phase. 9 Scanning and transmission electron microscopy (SEM and TEM) imaging gave further insights on how different CPEs and OPEs interact with the Gram-negative Escherichia coli ( E. coli ) bacteria in the dark. 9 To gain a deeper mechanistic understanding of the observed broad spectrum bactericidal activity of these compounds, we carried out a multiscale investigation in this study, from morphological scale to molecular level, to characterize the interactions of the CPE and OPE compounds with both Gram-positive and Gram-negative bacteria in the dark and with UV-irradiation.…”

Understanding the biocide action of poly(hexamethylene biguanide) using Langmuir monolayers of dipalmitoyl phosphatidylglycerol

“…CPEs and OPEs were shown to adsorb and penetrate into phosphatiylglycerol monolayers, even at high surface pressures as a result of electrostatic interaction between the positive polymer and the negative charge from the phospholipid [6,9]. With the importance of hydrophobic effects, the chain length is considered a relevant parameter for the resulting action of OPEs and CPEs [10], which is attributed to a carpet or detergent-like mechanism [11].…”