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Characterization of a novel two-partner secretion system implicated in the virulence of Pseudomonas aeruginosa
Laura M Faure1, Steve Garvis1, Sophie de Bentzmann1
1UMR7255, CNRS - Aix Marseille Université, 31 Chemin Joseph Aiguier, 13402 Marseille, France.
Abstract:
Pseudomonas aeruginosa is an opportunistic human pathogen implicated in nosocomial infection and infecting people with compromised immune systems such as cystic fibrosis patients. Although multiple genes involved in P. aeruginosa pathogenesis have been characterized, the overall mechanism of virulence is not fully understood. In this study, we identified a functional two-partner secretion (TPS) system, composed of the PdtA exoprotein and its cognate pore-forming β-barrel PdtB transporter, which is implicated in the virulence of P. aeruginosa. We found that the predicted PdtA exoprotein is related to the HMW-like adhesins subfamily TPS systems. We demonstrate here that limitation of inorganic phosphate (Pi) allows the production of PdtA protein. We show that PdtA is processed during its outer-membrane translocation, with an N-terminal domain released into the extracellular environment and a C-terminal domain associated with the outer membrane of the cell. We also obtained evidence that the transport of PdtA is strictly dependent on the production of PdtB, a result confirming that these proteins constitute a functional TPS system. Furthermore, using the Caenorhabditis elegans model of infection, we show that a pdtA mutant is less virulent than the wild-type strain.
Insights
Pseudomonas aeruginosa virulence involves a two-partner secretion (TPS) system. A functional TPS system, PdtA and PdtB, is crucial for P. aeruginosa pathogenesis and infection.
Area of Science:
- Microbiology
- Pathogenesis
- Molecular Biology
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen causing hospital-acquired infections.
- Its virulence mechanisms are not fully understood, especially in immunocompromised individuals like cystic fibrosis patients.
Purpose of the Study:
- To identify and characterize novel virulence factors in P. aeruginosa.
- To investigate the role of a specific two-partner secretion (TPS) system in P. aeruginosa pathogenesis.
Main Methods:
- Identification of a novel two-partner secretion (TPS) system (PdtA exoprotein and PdtB transporter).
- Analysis of PdtA protein production under inorganic phosphate (Pi) limitation.
- Demonstration of PdtA processing during outer-membrane translocation.
- Assessment of PdtA transport dependency on PdtB.
- Virulence testing using a Caenorhabditis elegans infection model.
Main Results:
- A functional TPS system, PdtA and PdtB, was identified and implicated in P. aeruginosa virulence.
- PdtA production is induced by inorganic phosphate (Pi) limitation.
- PdtA undergoes N-terminal extracellular release and C-terminal outer membrane association.
- PdtA transport is dependent on PdtB, confirming a functional TPS system.
- A pdtA mutant exhibited reduced virulence in a C. elegans infection model.
Conclusions:
- The PdtA/PdtB TPS system is a novel virulence factor for Pseudomonas aeruginosa.
- This system plays a significant role in P. aeruginosa pathogenesis, particularly under nutrient-limited conditions.
- Targeting this TPS system could offer new strategies for combating P. aeruginosa infections.
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