Amidine-Based Cationic Conjugated Oligoelectrolytes with Antimicrobial Activity against <i>Pseudomonas aeruginosa</i> Biofilms

Abstract

<i>Pseudomonas aeruginosa</i> is an opportunistic Gram-negative bacterium that can cause high-morbidity infections. Due to its robust, flexible genome and ability to form biofilms, it can evade and rapidly develop resistance to antibiotics. Cationic conjugated oligoelectrolytes (COEs) have emerged as a promising class of antimicrobials. Herein, we report a series of amidine-containing COEs with high selectivity for bacteria. From this series, we identified <b>1b</b> as the most active compound against <i>P. aeruginosa</i> (minimum inhibitory concentration (MIC) = 2 μg/mL) with low cytotoxicity (IC₅₀ (HepG2) = 1024 μg/mL). The activity of <b>1b</b> was not affected by known drug-resistant phenotypes of 100 diverse <i>P. aeruginosa</i> isolates. Moreover, <b>1b</b> is bactericidal with a low propensity for <i>P. aeruginosa</i> to develop resistance. Furthermore, <b>1b</b> is also able to inhibit biofilm formation at subinhibitory concentrations and kills <i>P. aeruginosa</i> in established biofilms. The <i>in vivo</i> efficacy of <b>1b</b> was demonstrated in biofilm-associated murine wound infection models.