Multiple Drugs that use big guns to shoot right through Tuberculosis
Allison White (12:00 Micro) found an article in Science Daily that describes work on tuberculosis from the University of Lausanne, France (EPFL). Because of the natural resistance to antibiotics, as well as rapidly spreading additional resistance genes in M. tuberculosis, traditional treatments are losing their efficacy. Here is Allie’s take on an alternative way to target this pathogen.
Over the past couple of decades tuberculosis claims many lives every year. The World Health Organization reports that last year there were around 8.6 million people affected by Tuberculosis. Even though Tuberculosis (TB) is not as prominent as many decades ago, it still effects a significant amount of people worldwide. TB Is caused by the bacteria Mycobacterium tuberculosis. One reason why tuberculosis still occurs in today’s society is because its cell wall’s contain mycolic acid that make it hard for antibiotics to get into the bacteria cells. Also tuberculosis is easily spread by close contact in the air we breathe infecting individual’s lungs which also makes it hard to treat and to contain. Doctors can prescribe antibiotics for TB but an issue that arises is that the bacteria becomes resistant after a long time of treatment. Because of this issue, lots of research is occurring on finding alternative. Researchers at EPFL over the past year have discovered two small molecules that have the potential to fight against Mycobacterium tuberculosis.
There are two main strategies that researchers have been tested in the lab which show great promise. One of most promising ideas includes the use of molecular machinery that TB uses to infect individuals. By using this machinery a team led by Stewart Cole at EPFL’s Global Health Institute were able to discover a drug-screening assay that has the capability to explore many compounds at the same time. Within the lab, these scientists take lug cells out of humans and grow them on special culture plates and infected all of them with TB. After doing this the scientists put different compounds into each of the culture plates to see what their effect on tuberculosis. Within the lab Cole’s team made sure they picked a compound that kills a protein called EsxA. By using the screening method, the researchers were able to narrow compounds down to two: BBH7 and BTP15. These compounds were able to halt the secretion of EsxA, even at low doses, which reduces its functionality of multiple components. This is not the only effect that BBH7 and BTP15 have on TB. These compounds also can reverse the depressing effects of TB on the immunity functions of infected cell. By doing this it can lead to the killing of the intracellular bacteria.
An important thing to note is the fact that this research is focusing on disarming the Mycobacterium tuberculosis so it is not able to damage lung cells rather than killing the Tb cells. The only downfall of this approach is that fact that you would be taking these compounds while using the original drugs to treat Tuberculosis. But if this is the only main downfall and it truly does stop TB cells from effecting our lung cells it is worth the risk and time. The compounds BBH7 and BTP15 would act against TB indirectly by helping the patient’s immune cells kill the bacteria. Using these compounds is different than using antibiotics, which effect the bacteria directly. Stewart Cole’s team is in the lab right now testing multiple combinations of the compounds to see if they can improve the effect that BBH7 and BTP15 have against TB. Their research gives us hope for the future and that Tuberculosis will soon be a disease of the past and not the future.