Incidence rates of tuberculosis have been subsiding worldwide in recent years, but a new challenge has cropped up--the emergence of TB strains that are resistant to current drugs.
What makes some forms of TB difficult to treat is that the bacterium can sit in a dormant, non-replicating state and create attack-resistant cell colonies called biofilms that contain a high proportion of non-replicating TB and are less susceptible to existing drugs. Another reason drug-resistant TB is on the rise is because patients often quit their medication regimen before completing their long courses of treatment and end up developing drug-resistant TB strains.
An international team of scientists at The Scripps Research Institute, the Howard Hughes Medical Institute and Albert Einstein College of Medicine of Yeshiva University has identified a promising new anti-TB compound designed to attacks the TB bacterium in two different ways.
Researchers screened 70,000 compounds and pinpointed one--called TCA1--that stood out for its ability to inhibit mycobacterial biofilms, which form in drug-resistant TB. In cell culture tests, TCA1 on its own killed more than 99.9% of ordinary, actively replicating TB bacteria within three weeks. When combined with isoniazid or rifampin, its effectiveness increased to 100% within that period. Against drug-resistant TB strains, TCA1 combined with isoniazid removed all signs of one common strain within a week. In mice, TCA1 was also effective at combating non-replicating TB, and animal studies suggest that a combo drug of TCA1 and isoniazid could be more powerful than existing therapies. TCA1 showed no sign of toxicity or adverse side effects in cell cultures and in mice, and the researchers believe there's nothing to suggest that the compound would induce drug resistance in TB.
TB infection rates have been curbed considerably in First World countries thanks to front-line medications like soniazid and rifampin, which came into use in 1952 and 1967 respectively. But the infection is still widespread throughout much of the globe. More than 2.2 billion people--a third of the world's population--are infected with Mycobacterium tuberculosis, the deadly bacterium that causes TB.
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