PA2146 Gene Knockout Is Associated With Pseudomonas aeruginosa Pathogenicity in Macrophage and Host Immune Response.

Pengfei She,Zubair Hussain,Linying Zhou,Zhen Luo,Yiqing Liu,Lihua Chen,Yong Wu

doi:10.3389/fcimb.2020.559803

Pengfei She, Zubair Hussain + Show 5 more

Open Access

https://doi.org/10.3389/fcimb.2020.559803

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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.

Highlights

Pseudomonas aeruginosa is a conditional pathogen that causes various infections in immunosuppressed patients (Mulcahy et al, 2014)
Pseudomonas aeruginosa secretes a variety of virulence factors and forms biofilms, which are mainly regulated by the quorum sensing (QS) system (Wang et al, 2020), and PA2146 was found to be a gene related to the QS system
Our results showed that the production of pyocyanin pigment was significantly higher in PAO1 PA2146 than in the PAO1 wild type strain (Figures 1B,C), indicating that PA2146 may interact with the QS system of P. aeruginosa

Summary

Introduction

Pseudomonas aeruginosa is a conditional pathogen that causes various infections in immunosuppressed patients (Mulcahy et al, 2014). P. aeruginosa can form biofilms on the surfaces of surgical instruments and human tissues, causing urinary tract infections, bone/joint infections, endocarditis, chronic wound infections, and cystic fibrosis, which are the major sources of morbidity and mortality in adults (Rineh et al, 2020). The main pathogenicity of P. aeruginosa may be due to the production of its virulence factors (including endotoxin and exotoxin) and subsequent pathological immune response. Exotoxin pyocyanin is one of the major virulence factors secreted by P. aeruginosa. Pyocyanin is regulated by the quorum sensing (QS) system, an important communication system that controls survival, virulence and biofilm formation in bacterial communities (Seleem et al, 2020). The hierarchical QS network plays a key role in the regulation of virulence gene expression (Wang et al, 2020)

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