title: Type II secretion system of Pseudomonas aeruginosa: in vivo evidence of a significant role in death due to lung infection.
abstract: BACKGROUND
  The role of toxins secreted by the type II secretion system (T2SS) of Pseudomonas aeruginosa during lung infection has been uncertain despite decades of research.
  
  
  METHODS
  Using a model of pneumonia in Toll-like receptor (TLR) 2,4(-/-) mice, we reexamined the role of the T2SS system. Flagellin-deficient mutants of P. aeruginosa, with mutations in the T2SS and/or T3SS, were used to infect mice. Mice were followed up for survival, with some killed at different intervals to study bacterial clearance, inflammatory responses, and lung pathology.
  
  
  RESULTS
  Strains carrying either secretion system were lethal for mice. Double mutants were avirulent. The T3SS(+) strains killed mice within a day, and the T2SS(+) strains killed them later. Mice infected with a strain that had only the T2SS were unable to eradicate the organism from the lungs, whereas those infected with a T2SS-T3SS double deletion were able to clear this mutant. Death caused by the T2SS(+) strain was accompanied by a >50-fold increase in bacterial counts and higher numbers of viable intracellular bacteria.
  
  
  CONCLUSIONS
  The T2SS of P. aeruginosa may play a role in death from pneumonia, but its action is delayed. These data suggest that antitoxin strategies against this organism will require measures against the toxins secreted by both T2SS and T3SS.
authors.affiliation: Department of Medicine, University of Florida, Gainesville, USA.
authors.forename: Jeevan
authors.initials: J
authors.lastname: Jyot
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Gregory
authors.initials: G
authors.lastname: Jouvion
authors.forename: Amrisha
authors.initials: A
authors.lastname: Verma
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.forename: Reuben
authors.initials: R
authors.lastname: Ramphal
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D005408:Flagellin / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D007113:Immunity, Innate; D007121:Immunocompetence; D008168:Lung / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018410:Pneumonia, Bacterial / Q000382:microbiology* / Q000401:mortality*; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology* / Q000401:mortality* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D012633:Secretin / Q000502:physiology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D005408:Flagellin; D012633:Secretin