Structural and Molecular Mechanism of CdpR Involved in Quorum-Sensing and Bacterial Virulence in Pseudomonas aeruginosa.
Although quorum-sensing (QS) systems are important regulators of virulence gene expression in the opportunistic human pathogen Pseudomonas aeruginosa, their detailed regulatory mechanisms have not been fully characterized. Here, we show that deletion of PA2588 resulted in increased production of pyocyanin and biofilm, as well as enhanced pathogenicity in a mouse model. To gain insights into the function of PA2588, we performed a ChIP-seq assay and identified 28 targets of PA2588, including the intergenic region between PA2588 and pqsH, which encodes the key synthase of Pseudomonas quinolone signal (PQS). Though the C-terminal domain was similar to DNA-binding regions of other AraC family members, structural studies revealed that PA2588 has a novel fold at the N-terminal region (NTR), and its C-terminal HTH (helix-turn-helix) domain is also unique in DNA recognition. We also demonstrated that the adaptor protein ClpS, an essential regulator of ATP-dependent protease ClpAP, directly interacted with PA2588 before delivering CdpR to ClpAP for degradation. We named PA2588 as CdpR (ClpAP-degradation and pathogenicity Regulator). Moreover, deletion of clpP or clpS/clpA promotes bacterial survival in a mouse model of acute pneumonia infection. Taken together, this study uncovered that CdpR is an important QS regulator, which can interact with the ClpAS-P system to regulate the expression of virulence factors and pathogenicity.
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi, China.
Jingru
J
Zhao
Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, China.|State Key Laboratory of Genetic Engineering, Innovative Collaborative Center of Genetics and Development, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China.
Xiang
X
Yu
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi, China.
Miao
M
Zhu
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi, China.
Huaping
H
Kang
State Key Laboratory of Genetic Engineering, Innovative Collaborative Center of Genetics and Development, Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, China.
Jinbiao
J
Ma
Department of Basic Science, School of Medicine and Health Science, University of North Dakota, Grand Forks, North Dakota, United States of America.
Min
M
Wu
Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, China.
Jianhua
J
Gan
TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, China.
Xin
X
Deng
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi, China.
Haihua
H
Liang
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D011487:Protein Conformation; D017510:Protein Folding; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D053038:Quorum Sensing; D014774:Virulence
D001426:Bacterial Proteins