Navigation Links
Study finds possible 'persistence' switch for tuberculosis
Date:9/17/2010

HOUSTON -- (Sept. 17, 2010) -- An examination of a portion of the tuberculosis genome that responds to stress has allowed Rice University bioengineers Oleg Igoshin and Abhinav Tiwari to zero in on a network of genes that may "switch" the disease into dormancy.

The bacteria that cause tuberculosis (TB), Mycobacterium tuberculosis, can transition into a dormant state to ward off attacks from antibiotics and the immune system. A new report from Igoshin and Tiwari in this month's issue of Physical Biology examines a network of genes that may make this possible. A computer model of the network showed it can act as a "persistence" switch that toggles the organism from a fast-growing to a slow-growing state.

"The molecular mechanisms that allow Mycobacterium tuberculosis to switch into this slow-growing, persistent state have been associated with genes that are activated when the microorganism is under stress," said Igoshin, senior author of the study and an assistant professor in bioengineering at Rice.

Tiwari, lead author of the study and a graduate student in Igoshin's lab, said, "We examined a stress-response network of genes that are found in both the TB bacterium and other closely related mycobacteria. We analyzed the role of multiple feedback loops in this network, and were eventually able to identify an ultrasensitive mechanism that works in combination with the feedback loops to form a switch. This switch can possibly activate transition to the persistent state."

The study was a collaborative effort between Igoshin's laboratory at Rice's BioScience Research Collaborative and the research groups of Gabor Balazsi at the University of Texas M.D. Anderson Cancer Center and Maria Laura Gennaro at the Public Health Research Institute of the New Jersey Medical School.

Scientists have long known that the TB bacterium has the ability to "hunker down" and go dormant under stressful conditions. Previous studies have confirmed that both the slow-growing and fast-growing forms of the bacteria have identical genes.

"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 readily adapted to other networks."

And that is precisely what Igoshin's lab and its collaborators are preparing to do thanks to a recently awarded five-year, $1.35 million grant from the National Institutes of Health (NIH).

"We want to understand -- at a network-level -- how different organisms mount these types of responses," Igoshin said. "We need this to better understand how cells function and to build better computer models of pathogenic bacteria that cannot be easily manipulated in the laboratory."


'/>"/>

Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

Related biology news :

1. Long-term study shows effect of climate change on animal diversity
2. £2 million study to reveal workings of dementia genes
3. New study looks to define evangelicals and how they affect polling
4. CU-Boulder study suggests air quality regulations miss key pollutants
5. Researchers study acoustic communication in deep-sea fish
6. Study reveals homeowner perceptions in fire-prone areas
7. Researchers study how pistachios may improve heart health
8. Study: urban black bears live fast, die young
9. New study indicates link between weight gains during pregnancy and dieting history
10. Study reveals specific gene in adolescent men with delinquent peers
11. Sweat it out: UH study examines ability of sweat patches to monitor bone loss
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study finds possible 'persistence' switch for tuberculosis
(Date:2/10/2017)... , Feb 10, 2017 ... new report "Personalized Medicine - Scientific and Commercial Aspects" ... ... personalized medicine. Diagnosis is integrated with therapy for selection of ... on early detection and prevention of disease in modern medicine. ...
(Date:2/8/2017)... , Feb. 8, 2017 About Voice Recognition ... to match it against a stored voiceprint template. ... pitch, cadence, and tone are compared to distinguish ... hardware installation, as most PCs already have a ... transactions. Voice recognition biometrics are most likely to ...
(Date:2/8/2017)... , Feb. 7, 2017 Report Highlights ... The global ... reach $11.4 billion by 2021, growing at a compound annual ... - An overview of the global markets for synthetic biology. ... estimates for 2016, and projections of compound annual growth rates ...
Breaking Biology News(10 mins):
(Date:3/23/2017)...  BioPharmX Corporation (NYSE MKT: BPMX), a specialty ... today reported financial results for the quarter and ... an update on the company,s clinical development efforts ... are pleased to report that last year was ... Anja Krammer. "We achieved key clinical milestones and ...
(Date:3/23/2017)... , March 23, 2017 According to a ... and derivatives market is fragmented due to the presence of a large ... Proliant, Thermo Fisher , and Sigma-Aldrich, compete with each other ... companies, collectively, held more than 76% of this market in 2016.  ... As of now, ...
(Date:3/22/2017)... March 22, 2017 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN), ... Center (RGC), U.K. Biobank and GSK to generate genetic sequence ... resource. The initiative will enable researchers to gain valuable insights ... a wide range of serious and life threatening diseases. ... Genetic evidence ...
(Date:3/22/2017)... CAMBRIDGE, Mass. , March 22, 2017 ... announced that it has eclipsed the 130 million covered ... Cross Blue Shield of Texas . ... stages, the Company continues to enjoy strong payor acceptance ... of its clinical programs and genetic counseling, its industry-leading ...
Breaking Biology Technology: