PA2146 Gene Knockout Is Associated With Pseudomonas aeruginosa Pathogenicity in Macrophage and Host Immune Response
Pengfei She1, Yiqing Liu1, Zhen Luo1
1Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, China.
Abstract:
Pseudomonas aeruginosa is a common gram-negative bacterium that usually causes nosocomial infection. The main pathogenicity of P. aeruginosa is caused by its virulence factors. PA2146 is reported to be a potential virulence-regulating gene and is highly expressed in the biofilms of P. aeruginosa. However, the effect of PA2146 mutant (PAO1ΔPA2146) on the macrophage immune response and murine models has not been reported. In the present study, PA2146 knockout was performed by homologous recombination. We found that PAO1ΔPA2146 stimulation significantly increased pyocyanin production but inhibited interleukin-6 secretion by neutrophils compared to PAO1 stimulation. In addition, PAO1ΔPA2146 treatment significantly inhibited cytokine production in macrophages independent of cell killing. In an acute pneumonia murine infection model, treatment with P. aeruginosa infected with PAO1ΔPA2146 inhibited cytokine secretion in the lungs but increased the infiltration of inflammatory cells compared to the wild-type group. The paradoxical results indicate that PA2146 deletion may also increase the production of virulence factors other than pyocyanin, which may not only increase inflammatory cell infiltration in the lungs but also lead to immune cells "shock." Overall, our findings suggest that PA2146 could serve as a P. aeruginosa virulence-regulating gene that regulates its macrophage and host immune response.
Insights
The Pseudomonas aeruginosa gene PA2146 regulates host immune responses. Deleting this gene impacts pyocyanin production and immune cell function in macrophages and neutrophils, affecting infection outcomes.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Pseudomonas aeruginosa is a gram-negative bacterium causing nosocomial infections.
- Bacterial virulence factors are key to P. aeruginosa pathogenicity.
- PA2146 is a potential virulence-regulating gene highly expressed in P. aeruginosa biofilms.
Purpose of the Study:
- To investigate the role of the PA2146 gene in P. aeruginosa virulence.
- To determine the effect of PA2146 knockout on macrophage immune response.
- To evaluate the impact of PA2146 mutant on murine models of infection.
Main Methods:
- Homologous recombination was used to create a PA2146 knockout mutant (PAO1ΔPA2146).
- Immune responses were assessed by measuring cytokine production (interleukin-6) in neutrophils and macrophages.
- An acute pneumonia murine infection model was used to study host-pathogen interactions.
Main Results:
- PAO1ΔPA2146 significantly increased pyocyanin production compared to wild-type PAO1.
- Neutrophil interleukin-6 secretion was inhibited by PAO1ΔPA2146 stimulation.
- Cytokine production in macrophages was significantly inhibited by PAO1ΔPA2146, independent of cell death.
- In a murine pneumonia model, PAO1ΔPA2146 infection inhibited lung cytokine secretion but increased inflammatory cell infiltration.
Conclusions:
- PA2146 deletion alters P. aeruginosa virulence factor production, including pyocyanin.
- The PA2146 gene plays a role in regulating the host immune response to P. aeruginosa infection.
- PA2146 is a potential target for modulating P. aeruginosa pathogenicity and host immune responses.
