Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in vivo

Abstract

The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa (P.a.). QS-controlled biofilm formation by P.a. in clinical settings has remained controversial due to emerging drug resistance. Our study demonstrates the ability of sub-minimum inhibitory concentrations of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of P.a. biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes and the expression levels of QS-regulatory genes, resulting in significant decreases in the QS signaling molecules. In a mouse peritoneal implant infection model, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological analyses revealed mitigation of the inflammatory response and reduced cell infiltration in the peritoneal tissue surrounding the implants after baicalin treatment. A reversed IFN-γ/IL-4 ratio were observed in the peritoneal lavage fluid of mice , indicating that baicalin treatment activated the Th1-induced immune response to expedite bacterial load clearance in vivo. Based on these results, baicalin might be a potent QS inhibitor and anti-biofilm agent for combating P.a. biofilm-related infections.