When Pamela A. Wearsch. Ph.D., was looking for an area of science to focus on that could have a major impact on global health, she chose TB (tuberculosis). This respiratory disease is caused by Mycobacterium tuberculosis, a type of bacteria that infects cells in the lungs. "TB is a leading cause of death worldwide from infectious disease," she says. "We really need to make progress in this area."
Dr. Wearsch, Assistant Professor in the Department of Pathology at Case Western Reserve University in Cleveland, Ohio, explains there are currently no vaccines that adequately protect against TB, and treatment poses a substantial burden to people with the disease. "A person must take several antibiotics for up to nine months, and these drugs can have side effects," she says.
Many people in underdeveloped countries develop active TB and start taking medications, but don't finish the course of treatment, either because of toxicity of the drugs or lack of accessibility. "When people don't take all of the medication, they aren't fully eradicating the infection. This can also fuel the emergence of drug-resistant strains of TB," she says.
As the incidence of drug-resistant TB increases, researchers need to be developing new tools now to treat the disease, Dr. Wearsch says. With a grant from the American Lung Association, she is studying tiny packets secreted by Mycobacterium tuberculosis called membrane vesicles that are thought to contribute to the survival of bacteria in the lungs.
"Mycobacterium tuberculosis infects immune cells in the lung called macrophages, which normally are ideal for clearing and killing pathogens. But Mycobacterium tuberculosis has figured out a way to infect this cell, and set up camp," Dr. Wearsch explains. "The bacteria have a lot of tricks that allow them to survive for decades in a person's body."
In the past several years, researchers, including those in Dr. Wearsch's lab, have found that many virulence factors, molecules that enable disease-causing bacteria to survive, are being sent out in groups in membrane vesicles, rather than being sent separately. "Many current drugs target one virulence factor at a time," she says. "We want to understand how the bacteria make these vesicles. Once we find out how this happens, then we can make drugs that will stop them from making the package. Then we aren't just taking out one soldier, but a whole army."
Her lab is studying a candidate gene that appears to play an essential role in the formation of vesicles in TB. The gene could be a potential target for TB therapy. "We want to see if the mutant TB bacteria that can't make vesicles can survive," Dr. Wearsch says. "We may see that these bacteria are quickly killed and cleared from the body."
Page last updated: March 2, 2020