Toothbrush tree fights Tuberculosis

M. Tuberculosis under scanning electron microscope
Courtesy of Kenneth Todar

A European consortium of researchers recently found a key protein in the South African Euclea natalensis, toothbrush tree, that inhibits the essential enzyme DNA gyrase in mycobacterium tuberculosis (TB). As more drug resistant strains of TB appear every year, new ways to combat the infection must be found. A Naphthoquinone from E. natalensis were found to bind a novel site on DNA gyrase, leaving TB unable to grow by blocking DNA replication.

TB is one of the most virulent infections currently alive as 2 billion people have been infected by the bacterium causing nearly 1 million deaths each year. Current treatments involve drawn out procedures, which sometimes end up breeding new resistant strains of TB. The naphthoquinone diospyrin found in the toothbrush tree, nick-named so because locals use its branches to make toothbrushes, was seen to inhibit DNA gyrase in a new way.

DNA gyrase is an enzyme found only in plants and bacteria that works to relax DNA supercoiling so that replication can take place. Here, researchers analyzed the efficacy of diospyrin in inhibiting gyrase in TB and haulting the bacterium’s growth.

Experiments narrowed the binding site of diospyrin to that of the B subunit of DNA gyrase near, but not on, the ATPase, energy releasing, structure of TB. The mode of action of diospyrin is unique compared to other antibacterials targeting DNA gyrase, therefore, more research is needed before this protein can be produced commercially to fight TB.

Diospyrin has showed promise in inhibiting TB thus far. After further experimentation and analysis, it may be more understood and ready to be used as a clinical means to fight M. tuberculosis.

Reference:
Shantanu Karkare, Terence T. H. Chung, Frederic Collin, Lesley A. Mitchenall, Adam R. McKay, Sandra J. Greive, Jacobus J.M. Meyer, Namrita Lall, Anthony Maxwell. The Naphthoquinone Diospyrin is an Inhibitor of DNA Gyrase with a Novel Mechanism of Action. Journal of Biological Chemistry, 2012.
http://dx.doi.org/10.1074/jbc.M112.419069

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