AUTHOR=Jin Yongxin , Zhang Mengjing , Zhu Feng , Peng Qianqian , Weng Yuding , Zhao Qiang , Liu Chang , Bai Fang , Cheng Zhihui , Jin Shouguang , Wu Weihui 

TITLE=NrtR Regulates the Type III Secretion System Through cAMP/Vfr Pathway in Pseudomonas aeruginosa

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.00085

DOI=10.3389/fmicb.2019.00085

ISSN=1664-302X

ABSTRACT=<p>The type III secretion system (T3SS) plays an important role in the pathogenesis of <italic>Pseudomonas aeruginosa</italic>. Expression of the T3SS is controlled under a complicate regulatory network. In this study, we demonstrate that NrtR (PA4916) is involved in the T3SS expression and pathogenesis of <italic>P. aeruginosa</italic> in a mouse acute pneumonia model. Overexpression of the T3SS central activator ExsA or exogenous supplementation of cAMP restored the expression of T3SS in the Δ<italic>nrtR</italic> mutant, suggesting that NrtR might regulate T3SS through the cAMP-Vfr signaling pathway. Further experiments demonstrated that the decrease of cAMP content is not due to the expression change of adenylate cyclases or phosphodiesterase in the Δ<italic>nrtR</italic> mutant. As it has been shown that <italic>nadD2</italic> is upregulated in the Δ<italic>nrtR</italic> mutant, we overexpressed <italic>nadD2</italic> in wild type PAK, which reduced the intracellular cAMP level and the expression of the T3SS genes. Meanwhile, deletion of <italic>nadD2</italic> in the Δ<italic>nrtR</italic> mutant restored the expression and secretion of the T3SS. Co-immunoprecipitation assay revealed an interaction between NadD2 and the catalytic domain of the adenylate cyclase CyaB. Further <italic>in vitro</italic> assay indicated that NadD2 repressed the enzymatic activity of CyaB. Therefore, we have identified a novel regulatory mechanism of T3SS in <italic>P. aeruginosa</italic>.</p>