New understanding of how two antibiotics attack drug-resistant strains of TB

24 Feb 2010

Paul Chinnock

Source: Nature Structural & Molecular Biology (see original article or PDF)

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Citation: Stanley RE, Blaha G, Grodzicki RL, Strickler MD, Steitz TA (2010). The structures of the anti-tuberculosis antibiotics viomycin and capreomycin bound to the 70S ribosome. Nat Struct Mol Biol. 2010 Feb 14. [Epub ahead of print]

New findings have improved understanding of how two drugs active against drug-resistant tuberculosis actually work. This will help in the development of new treatments for the disease.

The research was led by Yale University Professor Thomas Steitz, who won the Nobel Prize for Chemistry 2009. His team focussed on two antibiotics, viomycin and capreomycin, both of which belong to the tuberactinomycin family of antibiotics which are among the most effective antibiotics against multidrug-resistant tuberculosis (MDR-TB). Rates of MDR-TB are increasing worldwide and new drugs to fight this condition are urgently needed.

Like many antibiotics, viomycin and capreomycin are known to bind to the ribosomes of bacterial cells but the mechanism by which they do so has been unknown.The aim of the research was to determine how the antibiotics bind to the ribosome of Mycobacterium tuberculosis.

The research team made use X-ray crystallography, which enabled them to determine that the both antibiotics bind at the same site. This site or “binding spot” is between the large and small subunits of the ribosome. The binding spot was also found to be close to two sites where two other families of antibiotics (paromomycin and hygromycin B) are known to interact with the M. tb. ribosome.

With this new information, it may now be possible to develop new antibiotics active against MDR-TB and other infections. This development would be carried out by a US company Rib-X Pharmaceuticals Inc. Professor Steitz is a cofounder of the company, which has already used his earlier Nobel-prize winning findings on ribosome structure to develop a new generation of antibiotics to treat infections including methicillin-resistant Staphylococcus aureus (MRSA). The company has four other new antibiotics under development, two of which are in clinical trials.

Note: This research has been published in a journal that is not open access. To read the full paper a subscription to Nature Structural & Molecular Biology is therefore required. In some developing countries free access to the journal may be possible through HINARI.