, 2006; Pamp & Tolker-Nielsen, 2007). Moreover, swarming motility has been shown to be part of a complex differentiation process, which

leads to increased production of virulence factors and antibiotic resistance (Overhage et al., 2008). Swarming is dependent on functional quorum sensing (which induces the production of rhamnolipid), type IV pili and flagella (Kohler et al., 2000; Deziel et al., 2003). We have demonstrated recently that ginseng extract Y-27632 manufacturer reduces the production of signal molecules of quorum sensing (BHL and OdDHL) in supernatants of P. aeruginosa PAO1 cultures (Song et al., 2010). This finding may partly explain our results from the swarming tests in this study. However, the molecular mechanism of inhibition of swarming motility and induction of swimming and twitching motility by ginseng extract is

still unknown and needs further studies. In our animal study, pretreatment PLX4032 chemical structure with ginseng orally resulted in significantly higher phagocytosis rates and index in the BAL phagocytes from the wild-type P. aeruginosa PAO1-infected animals compared with saline-pretreated animals (Fig. 5a and b). In contrast, in the animals infected with flagella-deficient P. aeruginosa PAO1-filM, ginseng pretreatment did not improve the phagocytosis or the index. Clearly, the significantly increased phagocytosis rate and index in the PAO1-infected animals are due to the stimulation of P. aeruginosa PAO1 motility induced by ginseng in vivo. Previously, ID-8 we demonstrated in our animal models of chronic

P. aeruginosa lung infection that ginseng treatment results in faster bacterial clearance from the lungs and milder lung pathology when compared with the untreated animals (Song et al., 1997a, b, 1998). We also observed a significantly stronger neutrophil chemiluminescence in the blood, a shift of the immune response from a high anti-P. aeruginosa immunoglobulin G (IgG) response and local infiltration of mast cells in the lungs (T-helper type 2 response) to a TH1 immune response characterized by downregulation of IgG and upregulation of IgG2a levels, and improved functions of phagocytes by means of upregulated production of interferon-γ and downregulated interleukin-4 in the lung tissues and spleen (Song et al., 1997a, b, 1998, 2003, 2005). It has been well documented that a TH1 response favors host cleaning of infections by P. aeruginosa (Johansen et al., 1995, 1996., 1997; Moser et al., 1997, 2000, 2005). Our results from the present study suggest that ginseng induces increased bacterial motility in the biofilm-like alginate beads, resulting in the release of bacteria from the biofilm and loss of protective effects from the polymeric matrix, followed by an increased efficiency of the host immune system and antibiotics to clear the biofilm infection. The activation of the TH1 immune response induced by ginseng treatment and the increased motility of bacteria due to the effects of ginseng might exhibit a synergistic effect on the infection.