"The fact that the same organism can exist in two states at the same time in the same environment raises many questions," Igoshin said. "What is the basis for this bistability? What are the environmental cues that activate the switch?"
Other bacteria can switch between stable states as well, but Mycobacterium tuberculosis' ability to make this transition is one reason TB is such a widespread disease. As much as 30 percent of the world's population is believed to be infected with TB, which causes about 2 million deaths every year.
Igoshin said advances in molecular microbiology have allowed researchers to identify networks of mycobacterial genes that become activated when the organism is stressed. One of these networks contains genes that make mycobacterial transcription factor (MprA) and another protein called sigma factor E (SigE).
"Our collaborative team developed an approach that allowed us to formulate general conclusions about the properties of the mycobacterial stress-response network, even though we had limited knowledge of the underlying parameter values," Igoshin said.
Tiwari said, "Using this approach, we systematically examined the different modules, or subsets, of the full network. We found that bistability was linked to a positive feedback loop between MprA and SigE, a protein that binds to RNA polymerase to promote the production of both MprA and SigE."
Igoshin and Tiwari believe their modular approach to investigate the role of multiple feedback loops could also be used to unravel mechanisms that other bacteria use to control bistability.
"There are many outstanding questions regarding the specific ways that gene regulatory networks operate in bacteria," Igoshin said. "The generality of this modular approach opens up a promising avenue for answering some of those questions because it can be
|Contact: Jade Boyd|