Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Abstract

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against <i>Pseudomonas aeruginosa</i> from Chinese herbs and investigated baicalin from <i>Scutellariae radix</i> as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in <i>P. aeruginosa</i> was assessed using <i>luxCDABE</i>-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on <i>P. aeruginosa</i> pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in <i>P. aeruginosa</i>, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of <i>P. aeruginosa</i> on the mammalian cells and attenuated in vivo pathogenicity in a <i>Drosophila melanogaster</i> infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the <i>Pseudomonas</i> quinolone signal (PQS) system was found to be required for baicalin's impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating <i>P. aeruginosa</i> infections.