Salmonellaan infection that causes diarrhea, fever and abdominal pain, is the most common form of bacterial food poisoning in the US, sickening more than a million people each year. Although most healthy people recover without medical treatment, Salmonella The infection can spread throughout the body in young children, the elderly, and immunocompromised people and become a life-threatening infection. A new discovery sheds light on how it controls the human body Salmonella infections and open avenues for potential treatments for salmonella and other foodborne infections.
Research at the Robert Larner, MD College of Medicine at the University of Vermont has revealed details about the struggle for essential nutrients between Salmonella bacteria and the host during an infection. New evidence discovered by principal investigator Leigh Knodler, Ph.D., Professor of Microbiology and Molecular Genetics, and colleagues shows that specialized intestinal cells control the ability Salmonella to grow by limiting their access to essential minerals such as iron and manganese.
The epithelial cells that line the gut form a natural barrier to protect gut microbes from entering the bloodstream. But some harmful bacteria, such as e.g Salmonellacan breach this barrier and live inside these intestinal cells. In a study supported by a two-year R21 award from the National Institute of Allergy and Infectious Diseases (NIAID) published this week in The Proceedings of the National Academy of Sciencesa journal of the National Academy of Sciences (NAS), Knodler and colleagues found that intestinal epithelial cells pump iron and manganese away from the intracellular Salmonella to limit them growth in the intestine. This means that if pathogenic bacteria breach the intestinal barrier, then the host has a backup means of defense.
Using specialized fluorescent sensors of metal ion availability, Knodler and colleagues identified where metal limitation occurs in the gut during an infection and how human cells use a specialized system (a metal transporter) to retain these trace elements. The findings highlight a new dimension of host-pathogen interactions and suggest that manipulating metal transport pathways could enhance the body’s natural defenses. This new knowledge may lead to newer treatment or diagnostic options for Salmonella and other diarrheal and foodborne diseases.
All life forms, from bacteria to mammals, need essential trace elements. During an infection, there is a fierce biological tug-of-war between the human body and the microbes for these nutrients, and the outcome can determine the severity of the disease. Our research shows that intestinal epithelial cells use a metal transporter to starve Salmonella iron and manganese and limit bacterial growth. These transporters are potential drug targets for infectious and other human diseases, and our study lays the groundwork for understanding where and how they act in the body.”
Leigh Knodler, Ph.D., Professor of Microbiology and Molecular Genetics, University of Vermont
Next steps for research include examining additional metal transporters in the gut—of which there are dozens—to determine whether they also contribute to pathogen control and how they collectively shape the landscape of nutritional immunity. Study collaborators include researchers from the University of Wisconsin at Madison, Vanderbilt University Medical Center and John Salogiannis, Ph.D., at the Larner College of Medicine.
