title: A sensor kinase recognizing the cell-cell signal BDSF (cis-2-dodecenoic acid) regulates virulence in Burkholderia cenocepacia.
abstract: Burkholderia cenocepacia is an opportunistic human pathogen that uses cis-2-dodecenoic acid (BDSF) as a quorum-sensing signal to control expression of virulence factors. BDSF is a signal molecule of the diffusible signal factor (DSF) family that was first described in the plant pathogen Xanthomonas campestris. The mechanism of perception of this signal and the range of functions regulated in B. cenocepacia are, however, unknown. A screen for transposon mutants unable to respond to exogenous signal identified BCAM0227 as a potential BDSF sensor. BCAM0227 is a histidine sensor kinase with an input domain unrelated to that of RpfC, the DSF sensor found in xanthomonads. Transcriptome profiling established the scope of the BDSF regulon and demonstrated that the sensor controls expression of a subset of these genes. A chimeric sensor kinase in which the input domain of BCAM0227 replaced the input domain of RpfC was active in BDSF signal perception when expressed in X. campestris. Mutation of BCAM0227 gave rise to reduced cytotoxicity to Chinese hamster ovary cells and reduced virulence to Wax moth larvae and in the agar-bead mouse model of pulmonary infection. The findings identify BCAM0227 as a novel BDSF sensor and a potential target for interference in virulence-related signalling in B. cenocepacia.
authors.affiliation: BIOMERIT Research Centre, Department of Microbiology, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: McCarthy
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Kate B
authors.initials: KB
authors.lastname: Twomey
authors.forename: Andrea
authors.initials: A
authors.lastname: Sass
authors.forename: Tim
authors.initials: T
authors.lastname: Tolker-Nielsen
authors.forename: Eshwar
authors.initials: E
authors.lastname: Mahenthiralingam
authors.forename: J Maxwell
authors.initials: JM
authors.lastname: Dow
authors.forename: Robert P
authors.initials: RP
authors.lastname: Ryan
mesh_terms: D000818:Animals; D058491:Bacterial Load; D019121:Burkholderia Infections / Q000382:microbiology*; D057508:Burkholderia cenocepacia / Q000378:metabolism* / Q000472:pathogenicity*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004251:DNA Transposable Elements; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D000071677:Histidine Kinase; D008168:Lung / Q000382:microbiology; D051379:Mice; D009036:Moths; D016254:Mutagenesis, Insertional; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism*; D018085:Regulon; D015398:Signal Transduction; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014774:Virulence; D016959:Xanthomonas campestris / Q000235:genetics
chemical_list: C527562:2-dodecenoic acid; D004251:DNA Transposable Elements; D005229:Fatty Acids, Monounsaturated; D011494:Protein Kinases; D000071677:Histidine Kinase