Featured Research

from universities, journals, and other organizations

Ironing Out New Details Of Tuberculosis Infection

Date:
February 7, 2006
Source:
Howard Hughes Medical Institute
Summary:
Scientists in India, led by a Howard Hughes Medical Institute international research scholar, have identified five key genes that enable the bacterium that causes TB to acquire the iron it needs to sustain growth and promote infection.

Thin section transmission electron micrograph of Mycobacterium tuberculosis.
Credit: Image courtesy of Wadsworth Center, New York State Department of Health

Scientists in India, led by a Howard Hughes Medical Institute (HHMI) international research scholar, have identified five key genes that enable Mycobacterium tuberculosis to acquire the iron it needs to sustain growth and promote infection.

Related Articles


“Targeting genes within this cluster represents a good strategy for preventing tuberculosis and other mycobacterial infections,” said Rajesh S. Gokhale, an HHMI international research scholar at the National Institute of Immunology in New Delhi, India, and lead investigator on the study. “Because some of these genes are conserved across a number of related bacterial families, they are promising targets for drugs to treat TB and other bacterial diseases.”

The tuberculosis bacterium, which infects more than one third of the world's inhabitants, is a leading cause of death and disease worldwide.

Gokhale and colleagues report their findings in early online publication January 30, 2006, in the Proceedings of the National Academy of Sciences.

When M. tuberculosis infects humans, it takes up residence in immune cells called macrophages. To survive in this harsh environment, mycobacteria, like many other types of bacteria, need iron to carry out life-sustaining functions, such as creating proteins and synthesizing nucleotides to form DNA. However, free iron is not easily found in an intracellular environment. To obtain this rare element, most bacteria manufacture and secrete chemical compounds called siderophores that scavenge iron from the environment.

Researchers discovered siderophores—chemical compounds used by bacteria to scavenge iron from their cellular environment—well over 50 years ago, but the genes involved in adding the long-chain lipid anchor that enables M. tuberculosis to do so more efficiently, remained a mystery until now.

Mycobacteria have evolved siderophores with lipid-chain tails that enable them to exploit the macrophage's lipid-trafficking system to capture iron more efficiently. Instead of using siderophores that diffuse freely, mycobacteria anchor their siderophores to lipid membranes by means of a long fatty acid tail. After these siderophores bind to iron within the macrophage, the lipid tail makes the iron “sticky” enough to permit delivery to the very compartment in macrophages where the mycobacteria are lurking.

Using microarray data, the available literature, and intuition, Gokhale's group identified the location of the four genes that produce the lipid tail after observing that the expression of the genes significantly increased in response to low iron concentrations. The gene required for the synthesis of the siderophore core, called mbt-1, functions the same way, so Gokhale's team named the new locus mbt-2 and the new genes mbtK, mbtL, mbtM, and mbtN.

“Now that the major siderophore genes and their functions have been defined, understanding the biosynthetic pathway provides an opportunity to develop small-molecule inhibitors with the potential for developing anti-tuberculosis drugs,” said Gokhale. His team has already determined that some of genes from the mbt-2 cluster is conserved across several other bacterial species that cause various pulmonary, skin, and organ diseases. Since the mbt-1 genes are also conserved across many bacterial families, the mbt genes appear to be ideal antibacterial targets for treating tuberculosis and other bacterial infections, he said.


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Ironing Out New Details Of Tuberculosis Infection." ScienceDaily. ScienceDaily, 7 February 2006. <www.sciencedaily.com/releases/2006/02/060206234558.htm>.
Howard Hughes Medical Institute. (2006, February 7). Ironing Out New Details Of Tuberculosis Infection. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2006/02/060206234558.htm
Howard Hughes Medical Institute. "Ironing Out New Details Of Tuberculosis Infection." ScienceDaily. www.sciencedaily.com/releases/2006/02/060206234558.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins