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

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.559803

DOI=10.3389/fcimb.2020.559803

ISSN=2235-2988

ABSTRACT=<p><italic>Pseudomonas aeruginosa</italic> is a common gram-negative bacterium that usually causes nosocomial infection. The main pathogenicity of <italic>P. aeruginosa</italic> is caused by its virulence factors. <italic>PA2146</italic> is reported to be a potential virulence-regulating gene and is highly expressed in the biofilms of <italic>P. aeruginosa</italic>. However, the effect of <italic>PA2146</italic> mutant (PAO1Δ<italic>PA2146</italic>) on the macrophage immune response and murine models has not been reported. In the present study, <italic>PA2146</italic> knockout was performed by homologous recombination. We found that PAO1Δ<italic>PA2146</italic> stimulation significantly increased pyocyanin production but inhibited interleukin-6 secretion by neutrophils compared to PAO1 stimulation. In addition, PAO1Δ<italic>PA2146</italic> treatment significantly inhibited cytokine production in macrophages independent of cell killing. In an acute pneumonia murine infection model, treatment with <italic>P. aeruginosa</italic> infected with PAO1Δ<italic>PA2146</italic> inhibited cytokine secretion in the lungs but increased the infiltration of inflammatory cells compared to the wild-type group. The paradoxical results indicate that <italic>PA2146</italic> 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 <italic>PA2146</italic> could serve as a <italic>P. aeruginosa</italic> virulence-regulating gene that regulates its macrophage and host immune response.</p>