Pneumococcal Diseases

Using the Bodies Bile Salt in the Fight

Pneumococcal diseases are a major global public health problem, killing nearly a million people every year. They are caused by Streptococcus pneumoniae, or pneumococcus — a bacterium that is sometimes found in the nose and throat of healthy people who show no symptoms of illness. Pneumococci, however, can potentially lead to ear and sinus infections and life-threatening cases of pneumonia, meningitis and bacteremia. Young children, the elderly and the immune-compromised are at highest risk for severe cases.

Vaccines are currently available to help protect against pneumococcal diseases, but funding gaps leave millions unvaccinated and vulnerable, especially in the poorest communities worldwide. And while antibiotics are generally effective at treatment, about a third of cases now involve S. pneumoniae strains that are resistant to most commonly prescribed antibiotics.

As an associate professor at Rollins School of Public Health, Jorge Vidal, PhD proposed a new strategy to help in the fight against pneumococcal diseases using the bile salt sodium deoxycholate. Known as DocNa for short, this bile salt is a naturally occurring, metabolic byproduct of intestinal bacteria that aids in digestion. Vidal and his colleagues are investigating the potential of DocNa to prevent colonization of the respiratory tract with S. pneumoniae strains, a condition known as “carriage,” as well as to treat cases of infections.

“In order for pneumococcus to cause disease, it first has to colonize the nasal pharynx,” explains Vidal, a microbiologist trained in bacterial pathogenesis. “It’s estimated that in developed countries, the carriage rate for children ranges from around 25 to 40 percent. In developing countries, where many people live in crowded conditions, it can be as high as 90 percent. For reasons that are not well understood, in a small fraction of those with pneumococcus carriage in the nasal pharynx, the bacteria will migrate to the lungs or other areas of the body and cause disease.”

A bile solubility test is a method to diagnose S. pneumoniae carriage in an individual. First, a specimen from a nasal swab is placed in a petri dish and allowed to grow any bacteria it contains. Then DocNa, the sodium salt of deoxycholic acid, is added. DocNa bursts the cell membranes of S. pneumoniae while leaving similar, harmless bacteria intact. If a bacterial colony dies in the petri dish, that indicates the presence of S. pneumoniae.

Vidal began investigating whether DocNa could be used not just to test for S. pneumoniae but to prevent and treat the diseases it causes. He launched the project in his Rollins lab in 2018, after completing his training in the lab of Keith Klugman, a professor in Rollins’ Department of Global Health, focused on global molecular epidemiology of bacterial pathogens.

A recent paper by Vidal and his colleagues found that adding DocNa to the drinking water of mice colonized with S. pneumoniae reduced the population of the bacteria by 99 percent within 10 days. The researchers also demonstrated that DocNa kills multidrug-resistant S. pneumoniae strains without harming “good” bacteria.

The FDA has approved the use of injections of DocNa as a treatment to dissolve fat deposits in humans for cosmetic purposes, an encouraging sign that it could be safely used for other medicinal applications.

“Imagine repurposing an already FCA-approved drug, to treat infections — especially those that are drug resistant. That’s exactly what Jorge and his team are working on,” says Sat Balachander, a licensing associate in Emory’s Office of Technology Transfer who is working with Vidal on the possibility of using DocNa for this novel application.

Vidal envisions the possibility of one day using DocNa as a nasal spray or as an additive in an orally consumed product, such as toothpaste, to reduce S. pneumoniae carriage in humans. He also sees potential for DocNa to help in disease treatments. Using DocNa in combination with antibiotics, for instance, might make lower antibiotic dosages effective and help prevent S. pneumoniae strains from developing drug resistance.

Sinus Cavity

Vidal is now on the faculty of the University of Mississippi Medical Center. He and his collaborators are pursuing more studies in animal models to further characterize the mechanisms underlying how DocNa works against S. pneumoniae. If results continue to be encouraging, they hope to eventually advance the project to human trials.

“It is still early in the process but so far our results are very promising,” Vidal says. “Pneumococcal diseases are a major killer of people worldwide and we need new ways to prevent and treat them. An inexpensive, naturally occurring substance that doesn’t harm the body’s healthy flora may lead to an ideal way to save many lives.”

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