Ohio State’s John Gunn, PhD, vice chair and professor of Microbial Infection and Immunity, has received a bridge grant of $617,000 from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) to study of chronic infection of the gall bladder by salmonella. The grant could help millions of people in developing countries, as well as travelers.
Salmonella is bacteria that cause many diseases in humans and animals, including typhoid fever and gastroenteritis. Typhoid fever alone infects an estimated 21 million people a year, causing about 600,000 deaths worldwide. Salmonella also is highly correlated with liver, gallbladder bile duct and pancreatic cancer.
Typhoid fever is typically treated with antibiotics, but salmonellae (S. Typhi) are often resistant. Even with treatment, 2–3 percent of those infected die. In addition, many people infected with typhoid fever have no symptoms but become carriers, with the infection settling in their gall bladders.
“This high level of antibiotic resistance coupled with the recalcitrance of carriers to antibiotic treatment make new therapeutic options a high priority,” says Dr. Gunn. “Up to 5 percent of individuals infected with S. Typhi become chronic carriers, where the prime location of persistent infection is the gallbladder. Given the number of typhoid fever cases annually, there are up to 1 million carriers worldwide.”
This work is a continuation of Gunn’s previous gall bladder research. “We have demonstrated that gallstones aid in the development and maintenance of gall bladder carriage in a mouse model and in humans,” he said. “We know that the salmonellae attach to the gallstones and form a protective biofilm. However, the molecular basis of chronic carriage of salmonellae in the gall bladder is poorly understood.”
Researchers at Ohio State will study what enables the bacteria to colonize the gall bladder. They also will test therapeutics, including biofilm inhibitors and compounds to dissolve the gallstones, which would release the bacteria, making them susceptible to conventional antibiotics.
“With sustained funding, we could further develop our identified biofilm inhibitors and identify new targets from in vivo experiments that are crucial for the development and maintenance of carriage,” Gunn said. “Bench-to-bedside therapies take some time, but we are optimistic that we are on a fast track to real treatments that would aid S. Typhi chronic carriers.”