Bacteria that cause deadly pulmonary TB appear to promote their own spread by producing a cough-inducing molecule, new study by UTSW researchers proves. The results, published on the Cell network on March 5, 2020, could lead to new ways to prevent the spread of tuberculosis, which kills more than 1.5 million people a year worldwide.

Since ancient times, people have known that coughing is the main symptom of tuberculosis and that coughing contributes to the spread of the disease from person to person.. However, the cause of TB-related cough remains unclear, says study leader Michael Shiloh, MD, Associate Professor of Infectious Diseases at UTSW's Department of Internal Medicine and Department of Microbiology.. The prevailing hypothesis was that the cough is caused by infection-induced lung irritation and inflammation, but this has never been conclusively proven..

Shiloh and colleagues had a different idea: they hypothesized that the bacterial agent that causes tuberculosis, Mycobacterium tuberculosis, could itself produce a substance that triggers nerves in the airways that cause someone with the disease to cough, thereby allowing.

To test this idea, the team used guinea pigs, laboratory animals often used to study both tuberculosis and cough.. Although guinea pigs have been used as an experimental model for TB infection for over a century, it has not been clear whether the disease causes these animals to cough.. To answer this question, Shiloh and colleagues placed tuberculosis-infected guinea pigs in special chambers that recorded changes in pressure and volume caused by coughing.. Of course, TB-infected animals coughed significantly more than those free of TB..

To determine if the bacteria produce a substance that can cause coughing, the researchers isolated and tested various components of Mycobacterium tuberculosis in an attempt to determine if these components could do two things.. First, can the components themselves cause coughing in guinea pigs? And secondly, could the ingredients cause lab-grown pain-sensitive nerve cells - the type of cells responsible for stimulating coughs in the lungs - to behave as if they were triggered to trigger the cough reflex

After a series of experiments with components from Mycobacterium tuberculosis as well as from a wide range of other mycobacteria, Shilo's team eventually identified a mycobacterial cell surface fat molecule known as sulfolipid-1 (SL-1) as the main molecule that activates neurons.. lab grown. This response also occurred in human pain-sensitive nerve cells, suggesting that SL-1 and its function have been conserved through evolution among different mammalian species.. Importantly, when guinea pigs were exposed to purified SL-1, the animals actually coughed..

To show that SL-1 is the culprit in coughing, researchers infected guinea pigs with a genetically modified strain of Mycobacterium tuberculosis that cannot produce SL-1.. These guinea pigs developed all the typical symptoms of TB but did not cough, leading the research team to conclude that SL-1 is critical in triggering the cough during a TB infection..

However, Shilo says, the findings suggest that the bacteria that cause TB produce SL-1 primarily to stimulate the cough reflex to spread mycobacteria from infected to uninfected people.. Ultimately, he says, if research shows that cough suppression is not harmful to infected people, scientists may be able to develop a way to prevent transmission by counteracting SL-1 or preventing its production..

“In many places where TB is endemic, people with active TB are often not taken to the hospital, but simply sent home with antibiotics..

People can cough for months and spread the disease even when they receive appropriate treatment,” he says.. “Someday, doctors may give antibiotics in combination with a drug that prevents coughing, which in turn can prevent spread.”.

Conversely, he adds, this molecule could be used to help patients cough in conditions where it is beneficial, such as in cystic fibrosis or for patients who require breathing tubes.. Administration of a cough suppressant may help reduce the buildup of thick mucus in the patient's lungs.

medical-heal. en.