A sensor kinase recognizing the cell-cell signal BDSF (cis-2-dodecenoic acid) regulates virulence in Burkholderia cenocepacia
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A sensor kinase recognizing the cell-cell signal BDSF (cis-2-dodecenoic acid) regulates virulence in Burkholderia cenocepacia. / McCarthy, Yvonne; Yang, Liang; Twomey, Kate B; Sass, Andrea; Tolker-Nielsen, Tim; Mahenthiralingam, Eshwar; Dow, J Maxwell; Ryan, Robert P.
In: Molecular Microbiology, Vol. 77, No. 5, 2010, p. 1220-1236.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A sensor kinase recognizing the cell-cell signal BDSF (cis-2-dodecenoic acid) regulates virulence in Burkholderia cenocepacia
AU - McCarthy, Yvonne
AU - Yang, Liang
AU - Twomey, Kate B
AU - Sass, Andrea
AU - Tolker-Nielsen, Tim
AU - Mahenthiralingam, Eshwar
AU - Dow, J Maxwell
AU - Ryan, Robert P
PY - 2010
Y1 - 2010
N2 - SUMMARY 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 chimaeric 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 CHO 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.
AB - SUMMARY 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 chimaeric 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 CHO 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.
U2 - 10.1111/j.1365-2958.2010.07285.x
DO - 10.1111/j.1365-2958.2010.07285.x
M3 - Journal article
C2 - 20624216
VL - 77
SP - 1220
EP - 1236
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 5
ER -
ID: 22906169