One secret to how TB sticks with you

Jul 09, 2009

Mycobacterium tuberculosis is arguably the world's most successful infectious agent because it knows how to avoid elimination by slowing its own growth to a crawl. Now, a report in the July 10 issue of the journal Cell, a Cell Press publication, offers new insight into the bugs' talent for meager living.

"Tuberculosis can resist the host immune system and remain latent for decades," said Michael Glickman of the Memorial Sloan-Kettering Cancer Center. To do so, the mycobacterium responsible must resist an arsenal of DNA-damaging mutagens produced within the macrophage, the immune cell in which it lives. "It's incompletely understood how it can do that. We've identified one such mechanism."

The discovery could lead to new drugs that might eliminate strains of TB that have grown resistant to those that are currently available.

A whopping 30% of the world's population is infected with latent TB, the researchers said. In some people, the will reactivate, causing an estimated 1.3 million deaths a year, according to the World Health Organization.

One secret to TB's success is a protein that the researchers call CarD, the new study shows. That protein ratchets down transcription of the genes encoding ribosomal RNA (rRNA) by directly binding , the cellular machinery that transcribes DNA into RNA. rRNA is the central component of the ribosomes that serve as the cell's factories, and, Glickman explained, its production accounts for some 90 percent of all transcription.

"The mycobacterium tailors its translational machinery in response to stress within the host and we have identified CarD as a critical mediator of this response" he said.

Loss of CarD is fatal to M. tuberculosis living in cell culture, Glickman and his colleague Christina Stallings show. CarD depletion leaves the pathogen sensitive to killing by oxidative stress, starvation, and as it fails to cut its transcription of rRNA.

Importantly, Glickman said, they were able to show in infected mice that the mycobacterium depends on CarD not just when it is in its early, most active phase of growth, but also later in the course of infection. Drugs that target CarD's interaction with RNA polymerase could therefore lead to sorely needed, new TB drugs, the researchers said.

"The TB health crisis is exacerbated by the alarming emergence of multidrug- and extensively drug-resistant strains," Glickman said. "The development of new chemotherapeutic strategies is imperative, which requires insight into the pathways involved in M. tuberculosis infection, persistence, and drug resistance. CarD is one such pathway that we plan on targeting for therapeutic development. "

The findings might also prove to be clinically important for other disease-causing microbes.

Scientists knew before how some bacteria adapted to stress by limiting rRNA transcription, Glickman said. But the new study is the first to show how this is done in a mycobacterium, which lack a key gene responsible in other bugs like E. coli.

CarD is widely distributed in the bacterial world, he said, for instance it is found in Bacillus anthracis, the bacterium that causes anthrax. "This finding may have broader application to other important pathogens," he said.

Source: Cell Press (news : web)

Explore further: Fighting bacteria—with viruses

add to favorites email to friend print save as pdf

Related Stories

Smoking increases risk of TB infection, study finds

Feb 27, 2007

People who smoke have a greater risk of becoming infected with tuberculosis (TB) and of having that infection turn into active TB disease, according to an analysis by researchers at the University of California, Berkeley.

Tuberculosis drug shows promise against latent bacteria

Sep 12, 2008

A new study has shown that an investigational drug (R207910, currently in clinical trials against multi-drug resistant tuberculosis strains) is quite effective at killing latent bacteria. This revelation suggests that R207910 ...

Potential treatment for TB solves puzzle

Jul 04, 2008

Scientists have uncovered a new target for the potential treatment of TB, finally resolving a long-running debate about how the bacterial cell wall is built. The research, published in the July issue of Microbiology reveal ...

Recommended for you

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0