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Inhibition of virulence factor expression and swarming differentiation in Proteus mirabilis by p-nitrophenylglycerol
Shwu-Jen Liaw, H-C Lai1, S-W Ho1
1Graduate Institute of Microbiology, *School and Graduate Institute of Medical Technology, College of Medicine, National Taiwan University and †Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Abstract:
Proteus mirabilis is a common cause of upper urinary tract infections that can involve invasion of host urothelial cells. The ability to invade urothelial cells is coupled closely to swarming, a form of multicellular behaviour in which vegetative bacteria differentiate into hyperflagellate, filamentous swarming cells capable of co-ordinated and rapid population migration. Co-ordinate expression of virulence factors including urease, protease, haemolysin 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 growth rate, swarming/swimming activity, cell invasion ability and the ability to express various virulence factors were monitored in the presence or absence of PNPG. It was found that PNPG could inhibit the growth rate, swarming differentiation and swarming/swimming activities of P. mirabilis. The expression of virulence factors such as protease, urease, haemolysin and flagellin in P. mirabilis was also inhibited by PNPG. The ability of P. mirabilis to invade human urothelial cells was reduced dramatically in the presence of PNPG. These results suggest that PNPG has the potential to be developed as an agent active against the effects of P. mirabilis infection.
Insights
p-nitrophenylglycerol (PNPG) inhibits Proteus mirabilis swarming, a key factor in urinary tract infections. PNPG reduces bacterial growth, virulence factor expression, and urothelial cell invasion, suggesting its therapeutic potential.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Proteus mirabilis causes upper urinary tract infections by invading urothelial cells.
- Bacterial invasion is linked to swarming, a multicellular behavior involving differentiation into hyperflagellate, filamentous cells.
- Virulence factors like urease, protease, haemolysin, and flagellin are co-expressed during swarming.
Purpose of the Study:
- To investigate the effects of p-nitrophenylglycerol (PNPG) on P. mirabilis swarming-associated traits.
- To elucidate the relationships among swarming, virulence factor expression, and urothelial cell invasion.
- To assess PNPG's potential as an anti-infective agent.
Main Methods:
- Monitoring P. mirabilis growth rate, swarming/swimming activity, and urothelial cell invasion in the presence and absence of PNPG.
- Assessing the expression of virulence factors (urease, protease, haemolysin, flagellin) under PNPG treatment.
- Utilizing p-nitrophenylglycerol (PNPG) as a specific anti-swarming agent.
Main Results:
- PNPG significantly inhibited P. mirabilis growth rate and swarming/swimming activities.
- PNPG suppressed the expression of key virulence factors, including urease, protease, haemolysin, and flagellin.
- The invasion of human urothelial cells by P. mirabilis was dramatically reduced in the presence of PNPG.
Conclusions:
- PNPG effectively inhibits P. mirabilis swarming and associated virulence.
- PNPG reduces bacterial invasion of host cells, a critical step in pathogenesis.
- PNPG demonstrates potential as a therapeutic agent against P. mirabilis infections.