title: ChIP-seq reveals the global regulator AlgR mediating cyclic di-GMP synthesis in Pseudomonas aeruginosa.
abstract: AlgR is a key transcriptional regulator required for the expression of multiple virulence factors, including type IV pili and alginate in Pseudomonas aeruginosa. However, the regulon and molecular regulatory mechanism of AlgR have yet to be fully elucidated. Here, among 157 loci that were identified by a ChIP-seq assay, we characterized a gene, mucR, which encodes an enzyme that synthesizes the intracellular second messenger cyclic diguanylate (c-di-GMP). A ΔalgR strain produced lesser biofilm than did the wild-type strain, which is consistent with a phenotype controlled by c-di-GMP. AlgR positively regulates mucR via direct binding to its promoter. A ΔalgRΔmucR double mutant produced lesser biofilm than did the single ΔalgR mutant, demonstrating that c-di-GMP is a positive regulator of biofilm formation. AlgR controls the levels of c-di-GMP synthesis via direct regulation of mucR. In addition, the cognate sensor of AlgR, FimS/AlgZ, also plays an important role in P. aeruginosa virulence. Taken together, this study provides new insights into the AlgR regulon and reveals the involvement of c-di-GMP in the mechanism underlying AlgR regulation.
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Kong
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China.
authors.forename: Huaping
authors.initials: H
authors.lastname: Kang
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, Tianjin 300457, China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, 23 Hongda Street, Tianjin 300457, China dengxindx@gmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, ShaanXi 710069, China lianghh@nwu.edu.cn.
authors.forename: Haihua
authors.initials: H
authors.lastname: Liang
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D001665:Binding Sites; D018441:Biofilms / Q000254:growth & development; D047369:Chromatin Immunoprecipitation; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000096:biosynthesis; D029968:Escherichia coli Proteins / Q000235:genetics; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology; D011710:Pyocyanine / Q000096:biosynthesis; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014774:Virulence / Q000235:genetics
chemical_list: C110681:AlgR protein, Pseudomonas aeruginosa; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D015534:Trans-Activators; C062025:bis(3',5')-cyclic diguanylic acid; D011710:Pyocyanine; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP