title: Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease.
abstract: Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.
authors.affiliation: Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 263-8522, Japan. akiko@p.chiba-u.ac.jp
authors.forename: Akiko
authors.initials: A
authors.lastname: Takaya
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tabuchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Emiko
authors.initials: E
authors.lastname: Isogai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D054742:Acyl-Butyrolactones / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D049070:Protease La / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism; D011710:Pyocyanine / Q000378:metabolism; D053038:Quorum Sensing / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; C081237:LasI protein, Pseudomonas aeruginosa; C086515:RhlR protein, Pseudomonas aeruginosa; D014157:Transcription Factors; D011710:Pyocyanine; D049070:Protease La; D008025:Ligases; C096955:RHLI protein, Pseudomonas aeruginosa