title: The Lon protease is essential for full virulence in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa PAO1 lon mutants are supersusceptible to ciprofloxacin, and exhibit a defect in cell division and in virulence-related properties, such as swarming, twitching and biofilm formation, despite the fact that the Lon protease is not a traditional regulator. Here we set out to investigate the influence of a lon mutation in a series of infection models. It was demonstrated that the lon mutant had a defect in cytotoxicity towards epithelial cells, was less virulent in an amoeba model as well as a mouse acute lung infection model, and impacted on in vivo survival in a rat model of chronic infection. Using qRT-PCR it was demonstrated that the lon mutation led to a down-regulation of Type III secretion genes. The Lon protease also influenced motility and biofilm formation in a mucin-rich environment. Thus alterations in several virulence-related processes in vitro in a lon mutant were reflected by defective virulence in vivo.
authors.affiliation: Centre for Microbial Diseases & Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Elena B M
authors.initials: EB
authors.lastname: Breidenstein
authors.forename: Laure
authors.initials: L
authors.lastname: Janot
authors.forename: Janine
authors.initials: J
authors.lastname: Strehmel
authors.forename: Lucia
authors.initials: L
authors.lastname: Fernandez
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Taylor
authors.forename: Irena
authors.initials: I
authors.lastname: Kukavica-Ibrulj
authors.forename: Shaan L
authors.initials: SL
authors.lastname: Gellatly
authors.forename: Roger C
authors.initials: RC
authors.lastname: Levesque
authors.forename: Joerg
authors.initials: J
authors.lastname: Overhage
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000818:Animals; D002455:Cell Division; D002939:Ciprofloxacin / Q000494:pharmacology*; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D051379:Mice; D009154:Mutation; D049070:Protease La / Q000235:genetics / Q000378:metabolism; D011552:Pseudomonas Infections / Q000235:genetics / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051381:Rats; D014774:Virulence / Q000235:genetics
chemical_list: D002939:Ciprofloxacin; D049070:Protease La