Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 22, Pages 8018-8023Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0503022102
Keywords
Caulobacter; genetic circuit; hypoxia; signal transduction; two component
Categories
Funding
- NIGMS NIH HHS [R01 GM032506, GM32506, R37 GM032506] Funding Source: Medline
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Principles of modular design are evident in signaling networks that detect and integrate a given signal and, depending on the organism in which the network module is present, transduce this signal to affect different metabolic or developmental pathways. Here we report a global transcriptional analysis of an oxygen sensory/signaling network in Caulobacter crescentus consisting of the sensor histidine kinase FixL, its cognate response regulator FixJ, the transcriptional regulator FixK, and the kinase inhibitor FixT. It is known that in rhizobial bacteria these proteins form a network that regulates transcription of genes required for symbiotic nitrogen fixation, anaerobic and microaerobic respiration, and hydrogen metabolism under hypoxic conditions. We have identified a positive feedback loop in this network and present evidence that the negative feedback regulator, FixT, acts to inhibit FixL by mimicking a response regulator. Overall, the core circuit topology of the Fix network is conserved between the rhizobia and C crescentus, a free-living aerobe that cannot fix nitrogen, respire anaerobically, or metabolize hydrogen. In C crescentus, the Fix network is required for normal cellular growth during hypoxia and controls expression of genes encoding four distinct aerobic respiratory terminal oxidases and multiple carbon and nitrogen metabolic enzymes. Thus, the Fix network is a conserved sensory/signaling module whose transcriptional output has been adapted to the unique physiologies of C crescentus and the nitrogen-fixing rhizobia.
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