title: The CepIR quorum-sensing system contributes to the virulence of Burkholderia cenocepacia respiratory infections.
abstract: The cepIR genes encode an N-acyl homoserine lactone (AHL)-dependent quorum-sensing system consisting of an AHL synthase that directs the synthesis of N-octanoyl-L-homoserine lactone (ohl) and n-hexanoyl-L-homoserine lactone and a transcriptional regulator. The virulence of cepIR mutants was examined in two animal models. Rats were infected with agar beads containing Burkholderia cenocepacia K56-2, K56-I2 (cepI : : Tp(r)) or K56-R2 (cepR : : Tn5-OT182). At 10 days post-infection, the extent of lung histopathological changes was significantly lower in lungs infected with K56-I2 or K56-R2 compared to the parent strain. Intranasal infections were performed in Cftr((-/-)) mice and their wild-type siblings. K56-2 was more virulent in both groups of mice. K56-I2 was the least virulent strain and was not invasive in the Cftr((-/-)) mice. OHL was readily detected in lung homogenates from Cftr((-/-)) mice infected with K56-2 but was only detected at levels slightly above background in a few mice infected with K56-I2. Lung homogenates from mice infected with K56-2 had significantly higher levels of the inflammatory mediators murine macrophage inflammatory protein-2, KC/N51, interleukin-1beta and interleukin-6 than those from K56-I2-infected animals. These studies indicate that a functional CepIR quorum-sensing system contributes to the severity of B. cenocepacia infections. A zinc metalloprotease gene (zmpA) was shown to be regulated by CepR and may be one of the factors that accounts for the difference in virulence between the cepI mutant and the parent strain.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: P A
authors.initials: PA
authors.lastname: Sokol
authors.affiliation: Division of Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: U
authors.initials: U
authors.lastname: Sajjan
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: M B
authors.initials: MB
authors.lastname: Visser
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Gingues
authors.affiliation: Division of Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Forstner
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Kooi
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D019121:Burkholderia Infections / Q000382:microbiology*; D016956:Burkholderia cepacia / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D005798:Genes, Bacterial; D008297:Male; D045726:Metalloproteases / Q000235:genetics; D051379:Mice; D018181:Mice, Inbred CFTR; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012141:Respiratory Tract Infections / Q000382:microbiology*; D014774:Virulence / Q000235:genetics / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; C117246:CepR protein, Burkholderia; D004269:DNA, Bacterial; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D045726:Metalloproteases