Capsule Shedding and Membrane Binding Enhanced Photodynamic Killing of Gram-Negative Bacteria by a Unimolecular Conjugated Polyelectrolyte.

Abstract

The development of new antimicrobial agents to treat infections caused by Gram-negative bacteria is of paramount importance due to increased antibiotic resistance worldwide. Herein, we show that a water-soluble porphyrin-cored hyperbranched conjugated polyelectrolyte (<b>PorHP</b>) exhibits high photodynamic bactericidal activity against the Gram-negative bacteria tested, including a multidrug-resistant (MDR) pathogen, while demonstrating low cytotoxicity toward mammalian cells. Comprehensive analyses reveal that the antimicrobial activity of <b>PorHP</b> proceeds via a multimodal mechanism by effective bacterial capsule shedding, strong bacterial outer membrane binding, and singlet oxygen generation. Through this multimodal antimicrobial mechanism, <b>PorHP</b> displays significant performance for Gram-negative bacteria with >99.9% photodynamic killing efficacy. Overall, <b>PorHP</b> shows great potential as an antimicrobial agent in fighting the growing threat of Gram-negative bacteria.