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 Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-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 P. aeruginosa 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 P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster 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 Pseudomonas 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 P. aeruginosa infections.

Can We Arrest the Evolution of Antibiotic Resistance? The Differences between the Effects of Silver Nanoparticles and Silver Ions

“…34 T3SS is considered the most important virulence factor because it facilitates the transfer of bacterial effectors into eukaryotic host cells, prevents bacterial phagocytosis, expedites tissue invasion, and modulates the inflammatory response. 30 Interestingly, upon quinolone exposure, T3SS secretion has been reported to be induced, 35 unchanged, 19 and inhibited 36 by P. aeruginosa. At concentrations as low as 0.1 mM, copper ions, which are analogous to Ag + in many ways, were found to repress T3SS gene expression in P. aeruginosa.…”

Pharmacological effects of baicalin in lung diseases

“…Treatment with baicalin considerably lessened the severity of lung pathology and sped up the clearance of Pseudomonas aeruginosa from the lungs. After baicalin treatment, the Th1-induced inflammatory response and decreased cell infiltration in the lung around the implants were observed ( Zhang et al, 2021b ). In a different investigation, tobramycin treatment in combination with baicalin hydrate reduced the microbial load in mouse lungs infected with Burkholderia cenocepacia more than tobramycin treatment alone ( Brackman et al, 2011 ).…”

Research Progress on Antibiosis Activity of Scutellaria Flavonoids

“…In addition, baicalin attenuated the expression of 3-oxo-C12-HSL and C4-HSL of QS signaling [27]. Moreover, baicalin suppressed the functional genes of PA such as virulence genes,quorum sensing genes and motility related genes [28].…”