Poly (acetyl, arginyl) glucosamine disrupts <i>Pseudomonas aeruginosa</i> biofilms and enhances bacterial clearance in a rat lung infection model

<jats:title>Abstract</jats:title><jats:p><jats:italic>Pseudomonas aeruginosa</jats:italic> is a common opportunistic pathogen that can cause chronic infections in multiple disease states, including respiratory infections in patients with cystic fibrosis (CF) and non-CF bronchiectasis. Like many opportunists, <jats:italic>P. aeruginosa</jats:italic> forms multicellular biofilm communities that are widely thought to be an important determinant of bacterial persistence and resistance to antimicrobials and host immune effectors during chronic/recurrent infections. Poly (acetyl, arginyl) glucosamine (PAAG) is a glycopolymer which has antimicrobial activity against a broad range of bacterial species, and also has mucolytic activity which can normalize rheologic properties of cystic fibrosis mucus. In this study, we sought to evaluate the effect of PAAG on <jats:italic>P. aeruginosa</jats:italic> bacteria within biofilms <jats:italic>in vitro</jats:italic>, and in the context of experimental pulmonary infection in a rodent infection model. PAAG treatment caused significant bactericidal activity against <jats:italic>P. aeruginosa</jats:italic> biofilms, and a reduction in the total biomass of preformed <jats:italic>P. aeruginosa</jats:italic> biofilms on abiotic surfaces, as well as on the surface of immortalized cystic fibrosis human bronchial epithelial cells. Studies of membrane integrity indicated that PAAG causes changes to <jats:italic>P. aeruginosa</jats:italic> cell morphology and dysregulates membrane polarity. PAAG treatment reduced infection and consequent tissue inflammation in experimental <jats:italic>P. aeruginosa</jats:italic> rat infections. Based on these findings we conclude that PAAG represents a novel means to combat <jats:italic>P. aeruginosa</jats:italic> infection, which may warrant further evaluation as a therapeutic.</jats:p>