The BatR/BatS two-component regulatory system controls the adaptive response of Bartonella henselae during human endothelial cell infection.
Here, we report the first comprehensive study of Bartonella henselae gene expression during infection of human endothelial cells. Expression of the main cluster of upregulated genes, comprising the VirB type IV secretion system and its secreted protein substrates, is shown to be under the positive control of the transcriptional regulator BatR. We demonstrate binding of BatR to the promoters of the virB operon and a substrate-encoding gene and provide biochemical evidence that BatR and BatS constitute a functional two-component regulatory system. Moreover, in contrast to the acid-inducible (pH 5.5) homologs ChvG/ChvI of Agrobacterium tumefaciens, BatR/BatS are optimally activated at the physiological pH of blood (pH 7.4). By conservation analysis of the BatR regulon, we show that BatR/BatS are uniquely adapted to upregulate a genus-specific virulence regulon during hemotropic infection in mammals. Thus, we propose that BatR/BatS two-component system homologs represent vertically inherited pH sensors that control the expression of horizontally transmitted gene sets critical for the diverse host-associated life styles of the alphaproteobacteria.
Quebatte
Maxime
M
Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Dehio
Michaela
M
Tropel
David
D
Basler
Andrea
A
Toller
Isabella
I
Raddatz
Guenter
G
Engel
Philipp
P
Huser
Sonja
S
Schein
Hermine
H
Lindroos
Hillevi L
HL
Andersson
Siv G E
SG
Dehio
Christoph
C
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018416:Bartonella henselae / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D009876:Operon / Q000235:genetics; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001426:Bacterial Proteins; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins