Scientists discover how TB 'develops invincibility' against only available treatment

Mar 13, 2008

Scientists at the University of Leicester have uncovered a dramatic new twist in the battle against TB. They have identified how the killer bacterium makes itself immune to a key component of the only effective treatment against the disease.

Earlier this month, a separate team of TB researchers at Leicester announced a new advance in their fight against the resurgence of TB in Britain. They isolated the molecular ‘weapons’ of the bacterium and are assessing ways to make the bacterium impotent.

Now, in new research published in the Journal of Biological Chemistry, another team from the Departments of Biochemistry and Chemistry at the University has shown how the TB bacteria becomes resistant to one of the only available treatments for the killer disease.

Dr Peter Moody of the Biochemistry Department said: “Isoniazid is a pro-drug that an enzyme in the deadly bacteria itself makes active.

“Using the technique of protein crystallography and the incredibly bright X-ray source of the European Synchrotron at Grenoble, my team and that of Professor Emma Raven of the Chemistry Department at Leicester along with Dr Katherine Brown of Imperial College have shown how the pro-drug binds to two very similar enzymes - and from this we can see how mutations in the bacterial enzyme protect it from the treatment.”

This is the first time anyone has seen the way the pro-drug binds to activating enzymes.

Dr Moody said: "Drug-resistant forms of TB are approaching 10% of the 8000 cases a year in the UK, so understanding how this works is very important."

The researchers hope that this new understanding will help drug companies devise treatments for the resistant strains.

Dr Moody added: “Unfortunately, development of the UK synchrotron source (Diamond) is under threat because of the shortfall in funding, which could limit our ability to do this sort of fundamental medical research in the future”.

Citation: The Tuberculosis Prodrug Isoniazid Bound to Activating Peroxidases. Clive Metcalfe, Isabel K. Macdonald, Emma J. Murphy, Katherine A. Brown, Emma Lloyd Raven, and Peter C. E. Moody J. Biol. Chem., Vol. 283, Issue 10, 6193-6200, March, 2008

Source: University of Leicester

Explore further: Spy on penguin families for science

add to favorites email to friend print save as pdf

Related Stories

China demand to fuel Hong Kong iPhone grey market

8 hours ago

Wealthy mainland Chinese looking to buy the new iPhone 6 next week could expect to pay an eye-watering US$2,500 for the handsets in Hong Kong, following Apple's decision to delay the launch in China.

Netflix sets sights on European screens

8 hours ago

US online streaming giant Netflix will launch the second phase of its European expansion plan on Monday as it sets about seducing French viewers with a "House of Cards"-style drama set in Marseille.

Prosecutors target credit card thieves overseas

22 hours ago

Criminals from around the world buy and sell stolen credit card information with ease in today's digital age. But if they commit their crime entirely outside the United States, they may be hard to prosecute.

SpaceX's next cargo launch set for Sept 20

22 hours ago

SpaceX's next unmanned cargo trip to restock supplies at the International Space Station is scheduled for September 20, the US space agency said Friday.

Recommended for you

Transparent larvae hide opaque eyes behind reflections

1 hour ago

Becoming invisible is probably the ultimate form of camouflage: you don't just blend in, the background shows through you. And this strategy is not as uncommon as you might think. Kathryn Feller, from the University of Maryland ...

Peacock's train is not such a drag

2 hours ago

The magnificent plumage of the peacock may not be quite the sacrifice to love that it appears to be, University of Leeds researchers have discovered.

Iberian pig genome remains unchanged after five centuries

8 hours ago

A team of Spanish researchers have obtained the first partial genome sequence of an ancient pig. Extracted from a sixteenth century pig found at the site of the Montsoriu Castle in Girona, the data obtained indicates that ...

User comments : 0