Discovery of tuberculosis bacterium enzyme paves way for new TB drugs

Mar 27, 2009

A team of University of Maryland scientists has paved the way for the development of new drug therapies to combat active and asymptomatic (latent) tuberculosis infections by characterizing the unique structure and mechanism of an enzyme in M. tuberculosis, the bacterium that causes the disease. Assistant Professor of Chemistry and Biochemistry Barbara Gerratana, in the university's College of Chemical and Life Sciences, led the research team, which included her graduate student Melissa Resto and Assistant Professor Nicole LaRonde-LeBlanc.

"The NAD+ synthetase enzyme that our study describes is absolutely essential for the survival of the bacteria and an important drug target. We can now use the information we have about its structure and mechanism to develop inhibitors for this enzyme," Gerratana explained.

The study, titled "Regulation of active site coupling in glutamine-dependent NAD+ synthetase," was published in on March 8, 2009 in Nature Structural & Molecular Biology.

The development of new drugs to combat tuberculosis (TB) has become urgent, as strains of TB resistant to all major anti-TB drugs have emerged worldwide. The World Health Organization estimates that one third of the world's population is asymptomatically infected with TB and that ten percent will eventually develop the disease.

According to other leading TB researchers, these new findings from Gerratana and her colleagues will be extremely valuable for the design of structure-based inhibitors specific for M. tuberculosis NAD+ synthetase and may lead to the development of new drugs to combat and eliminate the disease.

"NadE [NAD+ synthetase] represents one of a small handful of TB drug targets that has iron-clad validation, the lack of a crystal structure was the only serious impediment to drug development and this study represents a hugely important step forward" said Clifton E. Barry, Chief of the Tuberculosis Research Section of the Intramural Research Division of the National Institute of Allergy and Infectious Diseases. "Inhibiting NadE even kills non-replicating cells, so this discovery may well benefit the one-third of the human population that carries latent bacteria."

NAD+ synthetase is responsible for making NAD+, a coenzyme found in all living cells that is involved in regulating many cellular processes and in reduction-oxidation metabolic reactions. More than one biosynthetic pathway is usually involved in NAD+ production. In humans, NAD+ can be obtained through several different complex pathways, and not all of the pathways utilize NAD+ synthetase to produce NAD+. Unlike in humans, however, there are only two pathways involved in producing NAD+ in the tuberculosis and both depend on the activity of NAD+ synthetase to obtain NAD+.

"We are optimistic about the potential for developing new drugs that will effectively target this enzyme in TB and minimize side effects to humans, since we have NAD+ biosynthetic pathways that are independent of the NAD+ synthetase activity," Gerratana said.

The World Health Organization reports that a new instance of TB infection occurs every second. Current treatment of tuberculosis targets the active tuberculosis bacterium and has little effect on the non-replicating bacterium. "If we don't tackle latent tuberculosis, this disease will not be eradicated," Gerratana said.

Source: University of Maryland (news : web)

Explore further: Researchers successfully clone adult human stem cells

add to favorites email to friend print save as pdf

Related Stories

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 ...

Experts say Toronto unprepared for TB

Feb 24, 2008

Health experts warn there could be an outbreak of tuberculosis in Toronto, which reportedly lacks a centralized system of TB clinics.

Experimental TB drug explodes bacteria from the inside out

Nov 27, 2008

An international team of biochemists has discovered how an experimental drug unleashes its destructive force inside the bacteria that cause tuberculosis (TB). The finding could help scientists develop ways to treat dormant ...

WHO warns of drug-resistant TB

Sep 06, 2006

The World Health Organization in Switzerland has warned of a new strain of tuberculosis that is rapidly spreading and cannot be treated with current drugs.

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.

Recommended for you

Researchers successfully clone adult human stem cells

Apr 18, 2014

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

Apr 18, 2014

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

Ashy
not rated yet Mar 28, 2009
There is NO tuberculosis bacteria, there is tuberculosis mycobacteria. Mycobacterias are unicellular, aerobic saprophytes, they eat only dead decomposing tissues. They can be found everywhere, but can't do something serious to living tissue.

Other question is what killed human tissue and make it food for mycobacterias. Presence of mycobacteria in TB is only symptom, like presence of temperature in flu.

More news stories

Biologists help solve fungi mysteries

(Phys.org) —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.