Hope For New Drug-Resistant TB Treatment From Bacterial Compound

on September 17 2012 5:01 PM
Reports of Drug-resistant Tuberculosis in India Have US CDC on Alert
A doctor (L) comforts her tuberculosis patient at the Indonesian Union Against Tuberculosis clinic in Jakarta, April 4, 2011. Tuberculosis remains a major global public health problem, with 9.4 million new cases and more than 1.7 million deaths recorded in 2009. Indonesia has the fifth highest tuberculosis rate in the world after India, China, South Africa and Nigeria based on 2009 World Health Organization (WHO) data. Reuters

A soil-dwelling bacteria may hold the key to a new drug that can combat tuberculosis, including strains of the disease that are able to evade current treatments.

Tuberculosis is caused by the bacteria Mycobacterium tuberculosis, and is spread when a person with the disease in their lungs or throat sneezes, coughs, or speaks. It claims nearly 2 million lives each year across the globe, with the highest concentrations of disease in Asia and sub-Saharan Africa. Plus, every year 500,000 people are infected by bacteria that are impervious to isoniazid and rifampin, the most widely used first-line treatments for TB, according to a recent paper in the New England Journal of Medicine.

In a paper published Monday in the journal EMBO Molecular Medicine, Swiss researchers reported their results of their investigation into pyridomycin, a compound made by the bacteria Dactylosporangium fulvum.

"Nature and evolution have equipped some bacteria with potent defense mechanisms to protect them against other bugs that share their habitat," senior author Stewart Cole said in a statement Monday. "Screening natural products generated by these organisms is therefore a powerful way to find possible new drugs to fight infectious diseases."

Scientists have known about pyridomycin's anti-bacterial properties for more than half a century, but the paper marks the first time any group has described how the compound attacks tuberculosis, according to the authors.

Pyridomycin's target is a protein called InhA, which is also targeted by isoniazid. But pyridomycin turns out to bind to InhA in a slightly different way that would allow it to get past the genetic defenses of tuberculosis bacteria that have mutated to avoid other treatments.

In the laboratory, pyridomycin killed the tuberculosis bacterium in clinical strains that were resistant to isoniazid, according to the paper.

Currently, some forms of multi-drug resistant tuberculosis can be treated with other drugs, or with chemotherapy, according to the World Health Organization.

"New diagnostics and therapeutics [for drug-resistant tuberculosis] are urgently needed; most of the methods used currently were developed decades ago," Harvard Medical School researcher Salmaan Keshvajee and Partners in Health founder Paul Farmer wrote in the NEJM on September 6.

Pyridomycin could possibly fit the bill.

SOURCE: Hartkoorn et al. "Towards a new tuberculosis drug: pyridomycin - nature's isoniazid." EMBO Molecular Medicine published online 17 Sept 2012.

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