"What we think is that having gallstones makes you more susceptible to becoming a carrier because it provides that environment for Salmonella to bind to the surface, form a biofilm and establish infection," Gunn said. "Whether that happens 100 percent of the time, nobody knows."

In a second component of the mouse study, the researchers tested fresh fecal pellets from infected mice to test the association between gallstone biofilms and transmission of a typhoid-like infection via feces, a phenomenon called "shedding." The mice with gallstones shed three times more bacteria than did infected mice without gallstones.

"The mice that had gallstones and were infected with bacteria had a much higher rate of shedding, meaning those bacteria were released, probably because they had more bacteria in the gallbladder itself," Gunn said.

The mouse data not only supported Gunn's hypothesis that gallstones present at least one surface on which Salmonella biofilms form and maintain the carrier state of typhoid fever. The researchers also realized they had developed a new mouse model for further study of asymptomatic typhoid carriage.

Gunn and colleagues also obtained data from humans at a hospital in Mexico whose gallbladders were removed as a treatment for gallstone complications. Though none of the patients had ever shown symptoms for typhoid fever, 5 percent of them ended up being carriers of Salmonella Typhi bacteria biofilms on their gallstones. In the single patient determined to be a typhoid carrier who didn't have biofilm on his gallstones, the stones were dark in color, suggesting they were likely composed of something other than cholesterol, Gunn said.

This ability of a single individual to harbor latent bacteria elsewhere in the gallbladder leads Gunn and colleagues to suspect that biofilms can form elsewhere in the gallbladder - perhaps in its lining or persisting within specific cells of the gallbladder wall. Gunn's lab is exploring those possibilities.

This work is supported by the National Institutes of Health and a graduate education fellowship from Ohio State's Public Health Preparedness for Infectious Diseases initiative.

Co-authors of the study are Robert Crawford of the Center for Microbial Interface Biology and Department of Molecular Virology, Immunology and Medical Genetics at Ohio State; Roberto Rosales-Reyes and Mar-a de la Luz Ram-rez-Aguilar of the Universidad Nacional Autonoma de Mexico; Oscar Chapa-Azuela of Hospital General de Mexico; and Celia Alpuche-Aranda of the Instituto Nacional de Referencia Epidemiologica in Mexico.

Contact: John Gunn, (614) 292-6036; gunn.43osu Emily Caldwell, (614) 292-8310; caldwell.151osu

Source: Ohio State University