Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify the pattern of gene-expression changes for tuberculosis in a living host

22.03.2004


Researchers at the Center for Biomedical Inventions at UT Southwestern Medical Center at Dallas have identified the genetic changes that Mycobacterium tuberculosis, the bacterium that causes tuberculosis, undergoes during infection of a living host.

For the first time, researchers have adapted gene-chip technology to carry out genomic analysis of gene expression during the course of infection not only for M. tuberculosis, but for any pathogen. The findings will appear in an upcoming issue of the Proceedings of the National Academy of Sciences and are currently available online.

To analyze multiple questions about the pathogenesis of tuberculosis, the researchers used gene chips, which allowed them to assess the pattern in which bacterial genes are expressed during the course of infection. This work demanded two years of technology development to establish a protocol that allowed high-throughput analysis of genes that were expressed in a pathogen that was extracted from an infected animal, rather than simply grown in culture.



"This is an example of how the high-throughput system is a new avenue to study a variety of pathogens and how they affect living hosts," said Dr. Stephen Albert Johnston, director of the CBI and one of the senior authors of the study. "We see it as a tool for vaccine and drug development against disease and the threat of biological weapons."

In the PNAS paper, researchers discuss how the tuberculosis bacterium had previously undergone genetic analysis based only on lab tests outside of a living organism. Once the entire genome of M. tuberculosis was sequenced, Drs. Johnston and Adel Talaat, then a postdoctoral researcher at UT Southwestern, began using high-speed microarray techniques, or gene-chip technology, to analyze the bacterium’s gene expression at different stages of infection in mice.

Since other pathogens have been sequenced, Dr. Johnston and coworkers are now genetically analyzing anthrax and plague infection in in vivo animal models, gaining more insight into how the potential bioweapons might behave in humans. The genetic analysis also could be applied to previously unknown diseases, like SARS.

"By identifying the genes that cause disease progression in vivo, we can begin to piece together the knowledge that will allow us to discover better targets for drug therapies," said Dr. Johnston.

To study tuberculosis – it annually kills about 2 million people around the world – researchers analyzed the bacterium’s gene activity in healthy mice, in mice with compromised immune systems, and in lab cultures. They looked at which genes were active and at what stages of the infection, from the first day to several weeks after exposure.

They discovered that a specific set of tuberculosis genes was activated only in healthy mice 21 days after the initial infection, a critical time in the progression of the disease in humans and other animals. This indicates that these genes are activated to help the pathogen survive within the host.

"We found that some genes are turned down so they stay below the immune system’s radar," said Dr. Johnston, professor of microbiology. "The bug (tuberculosis) acts in a stealthy way, hoping not to become a target of the host’s immune system but needing to stay just active enough to continue surviving."

Some genes were expressed only if the pathogen was active in an animal model. Infection in lab cultures – previously the only way that tuberculosis has been studied at the genetic level – did not express the same genetic responses in the tuberculosis pathogen. The new findings indicate that infectious diseases need to be studied in live animals models if meaningful results are to be attained.

"Understanding bacterial gene expression in vivo is central to our understanding of how bacteria colonize, invade and interact with or disrupt the normal host-cell functions and eventually produce disease," the researchers write.


###
The study was funded by the National Institutes of Health and Defense Advanced Research Projects Agency. This work was carried out in collaboration with the Animal Model Development Center at the University of New Mexico Health Science Center.

Steve O’Brien | EurekAlert!
Further information:
http://www.swmed.edu/

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>