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They realized what causes TB sufferers to cough

Tuberculosis is responsible for the deaths of more than 1.5 million people worldwide each year. It has been known since ancient times that coughing is the primary symptom of tuberculosis and that coughing allows the disease to spread from person to person.

However, the cause of tuberculosis-related cough is not yet clear. The prevailing hypothesis so far has been that the cough is caused by lung irritation and inflammation caused by infection, but this has not yet been conclusively proven. Progress is now made!

The bacteria that cause tuberculosis has been shown to facilitate its spread by producing a molecule that causes coughing, according to a new study by researchers at UTSW (Research Institute in Dallas) led by Michael Shiloh, MD, PhD, of UTSW Internal Medicine, an associate professor in the Department of Diseases. Infectious and Microbiology Department.

Researchers infected guinea pigs

To test this, the research team conducted experiments on guinea pigs. These animals are often used in laboratory conditions to study both tuberculosis and cough. Although they have been used as an experimental model for more than a century, it is not clear if the disease will cause them to cough. To answer this question, Shiloh and colleagues placed guinea pigs infected with tuberculosis in special chambers that recorded changes in pressure and volume due to coughing. Animals infected with tuberculosis coughed significantly more than those without tuberculosis.

To determine whether bacteria produce a cough-stimulating substance, researchers isolated and tested different components of Mycobacterium tuberculosis and attempted to determine if these components were capable of two things. First, do the ingredients cough up on their own, and second, are the substances identified by the researchers able to activate pain-sensing neurons that stimulate coughing or elicit a cough reflex in the lungs?

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In experiments with components of Mycobacterium tuberculosis and other Mycobacterium species, Shiloh’s research team identified a cell surface lipid of mycobacteria, a molecule already known as sulfolipid-1 (SL-1), as a neurostimulant. This response also occurred in human pain-sensing neurons, indicating that SL-1 and its function have been conserved throughout evolution in various mammalian species. As evidence, when guinea pigs were exposed to purified SL-1, the animals actually started to cough.

To demonstrate that SL-1 is indeed responsible for coughing, researchers infected guinea pigs with a genetically modified strain of Mycobacterium tuberculosis that cannot produce SL-1. These guinea pigs showed all the typical symptoms of tuberculosis but did not cough! Taken together, Shiloh said, the results mean that the bacteria that cause tuberculosis primarily produce SL-1 to stimulate the cough reflex so that mycobacteria can spread from infected people to uninfected people.

If science shows that suppressing a cough is not harmful to infected individuals, Shiloh hopes that scientists can prevent the spread of infection by developing a way to block SL-1 production, or somehow they can counteract the effect of coughing.

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