Inhibition of virulence factor expression and swarming differentiation in Proteus mirabilis by p-nitrophenylglycerol

Proteus mirabilis is a common cause of upper urinary tract infections that can involve invasion of host urothelial cells. The ability to invade urothe lial cells is coupled closely to swarming, a form of multicellular behaviou r in which vegetative bacteria differentiate into hyperflagellate, filament ous swarming cells capable of co-ordinated and rapid population migration. Co-ordinate expression of virulence factors including urease, protease, hae molysin and flagellin during swarm-cell differentiation in P. mirabilis has been reported. To investigate the effects of p-nitrophenylglycerol (PNPG), a potent anti-swarming agent, on the various swarming-associated traits of P. mirabilis and to elucidate the relationships among them, P. mirabilis g rowth rate, swarming/swimming activity, cell invasion ability and the abili ty to express various virulence factors were monitored in the presence or a bsence of PNPG, It was found that PNPG could inhibit the growth rate, swarm ing differentiation and swarming/swimming activities of P. mirabilis. The e xpression of virulence factors such as protease, urease, haemolysin and fla gellin in P. mirabilis was also inhibited by PNPG. The ability of P. mirabi lis to invade human urothelial cells was reduced dramatically in the presen ce of PNPG, These results suggest that PNPG has the potential to be develop ed as an agent active against the effects of P. mirabilis infection.