title: The Pseudomonas aeruginosa global regulator VqsR directly inhibits QscR to control quorum-sensing and virulence gene expression.
abstract: The opportunistic pathogen Pseudomonas aeruginosa has at least three quorum-sensing (QS) systems, including the acyl-homoserine lactone (acyl-HSL)-mediated las and rhl systems, as well as the 2-alkyl-4(1H)-quinolone (AHQ) signal-based system. A group of key regulators of these QS systems have been identified, such as qteE, vqsM, vqsR, and vfr. However, the underlying regulatory mechanisms of these QS systems are not yet fully understood. Here, using electrophoretic mobility shift assays, we demonstrated that VqsR indirectly regulates acyl-HSL systems but specifically binds to the qscR promoter region, which indicates that VqsR influences QS-controlled pathways through QscR. Through a dye-based DNase I footprint assay, we showed that VqsR interacts with an inverted repeat (IR) motif (TCGCCN(8)GGCGA, where N is any nucleotide) in the promoter region of qscR. A genome-wide search identified 50 other promoter regions carrying the same putative IR motif. The recombinant VqsR protein exists as a homodimer in solution. In addition, using a qscR-lux reporter assay and Northern blot hybridization, we found that the transcription level of qscR increased 4-fold in the vqsR deletion strain compared to the wild-type PAO1 strain, indicating vqsR as a negative regulator of qscR. Taken together, these findings provide new insights into the complex regulation network of QS systems in P. aeruginosa.
authors.affiliation: Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, China. hhliang@uchicago.edu
authors.forename: Haihua
authors.initials: H
authors.lastname: Liang
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Ji
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
authors.forename: Tuo
authors.initials: T
authors.lastname: Shen
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001665:Binding Sites; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055503:Protein Multimerization; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000502:physiology; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000037:antagonists & inhibitors*; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; C434259:QscR protein, Pseudomonas aeruginosa; D012097:Repressor Proteins; D037521:Virulence Factors