Our laboratory studies the general stress response in Bacillus subtilis, a unicellular bacterium which is accessible to genetic manipulation. This response is triggered by diverse stresses to enhance survival in the natural environment, in fresh and processed foods, in medical facilities, and in pathogenic interactions.
Among Bacillus subtilis and related Gram positive bacteria, the general stress response is governed by the sigma-B (sB) transcription factor. Loss of sigma-B function causes increased sensitivity to multiple stresses, including acid, antibiotic, heat, osmotic, and oxidative stress.
Our goal is to understand this response using B. subtilis as a model, beginning with the sensors that detect the different stresses, extending through the signal transduction network that conveys these stress signals to sigma-B, and ending with the physiological role of the 200 or more genes under sigma-B control. A significant theme in our research is the use of a combined approach that employs genetics, biochemistry, molecular biology, and DNA arrays.
Of the questions we address, investigation of the signal transduction network is the most advanced. The network functions by a "partner switching" mechanism in which key protein interactions are controlled by serine and threonine phosphorylation. This mechanism appears to be very ancient, very plastic, and widespread among the eubacteria. Here it is found in two distinct signaling branches which converge on sigma-B -- one specific for energy stresses and the other specific for environmental stresses. Click model for a description of the current model of the sigma-B signal transduction network.
Among bacteria closely related to B. subtilis, sigma-B and its associated regulators are now known to be important for stress resistance in the human pathogens Listeria monocytogenes and Staphylococcus aureus. Moreover, sigma-B function directly contributes to virulence in Bacillus anthracis and to the ability of Staphylococcus epidermidis and S. aureus to form adherent biofilms, which is crucial component of their proclivity to cause infections via medical devices. And among the high-GC Gram positive bacteria, a sigma-B-like factor is important for virulence in Mycobacterium tuberculosis. In light of these findings, the use of B. subtilis as a model to understand the general stress response has assumed considerable significance.
