Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection

Abstract

Virulent factors produced by pathogens play an important role in the infectious process, which is regulated by a cell-to-cell communication mechanism called quorum sensing (QS). Pseudomonas aeruginosa is an important opportunistic human pathogen, which causes infections in patients with compromised immune systems and cystic fibrosis. The QS systems of P. aeruginosa use N-acylated homoserine lactone (AHL) as signal molecules. Previously we have demonstrated that Panax ginseng treatment allowed the animals with P. aeruginosa pneumonia to effectively clear the bacterial infection. We postulated that the ability to impact the outcome of infections is partly due to ginseng having direct effect on the production of P. aeruginosa virulence factors. The study explores the effect of ginseng on alginate, protease and AHL production. The effect of ginseng extracts on growth and expression of QS-controlled virulence factors on the prototypic P. aeruginosa PAO1 and its isogenic mucoid variant (PAOmucA22) was determined. Ginseng did not inhibit the growth of the bacteria, enhanced the extracellular protein production and stimulated the production of alginate. However, ginseng suppressed the production of LasA and LasB and down-regulated the synthesis of the AHL molecules. Ginseng has a negative effect on the QS system of P. aeruginosa, may explain the ginseng-dependent bacterial clearance from the animal lungs in vivo in our previous animal study. It is possible that enhancing and repressing activities of ginseng are mutually exclusive as it is a complex mixture, as shown with the HPLC analysis of the hot water extract. Though ginseng is a promising natural synergetic remedy, it is important to isolate and evaluate the ginseng compounds associated with the anti-QS activity.

Fig. 1

Growth curves of P. aeruginosa. The prototypic PAO1 (A) and PDO300 (B) were grown in the absence (X) and presence of 1.25% (open circle), 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 1

Growth curves of P. aeruginosa. The prototypic PAO1 (A) and PDO300 (B) were grown in the absence (X) and presence of 1.25% (open circle), 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 2

Alginate production in P. aeruginosa. The amount of alginate produced in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng were quantified.

Fig. 3

Effect of ginseng on P. aeruginosa PAO1 protease activities. The staphylolytic LasA (A) and elastolytic LasB (B) activities were monitored in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 3

Effect of ginseng on P. aeruginosa PAO1 protease activities. The staphylolytic LasA (A) and elastolytic LasB (B) activities were monitored in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 4

Extracellular protein levels in P. aeruginosa PAO1. The protein levels in the supernatant were quantified in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 5

AHL production in P. aeruginosa PAO1. The BHL (A) and OdDHL (B) levels in the supernatant were quantified in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 5

AHL production in P. aeruginosa PAO1. The BHL (A) and OdDHL (B) levels in the supernatant were quantified in the absence (X) and presence of 2.5% (filled circle) and 5% (diamonds) of ginseng.

Fig. 6

HPLC - UV analysis of ginseng extract. The chromatogram show combined ginsenoside standards (A) and aqueous ginseng extracts (B). Peaks are a function of intensity measured in milliabsorption units over time in minutes. Peaks corresponding to the six ginsensosides used as standards are labeled.