Grant: Project Grant

Bacterial infections in the bloodstream are a serious health problem, especially as antibiotic resistance continues to rise. Among the many bacteria that cause these infections, Salmonella is particularly concerning because it has an unusual ability to avoid detection and removal by the immune system. In most cases, a specialized group of immune cells in the liver, called Kupffer cells, act as a frontline defense by trapping and eliminating bacteria from the blood. However, Salmonella has developed a unique way to escape this process, unlike other harmful bacteria such as E. coli and Staphylococcus aureus, which are quickly cleared. Our research has shown that a specific part of Salmonella's outer surface, called the O-antigen, plays a critical role in helping it survive in the bloodstream. When we remove this O-antigen, Salmonella is rapidly caught and destroyed by Kupffer cells, suggesting that the O-antigen helps it evade immune defenses. However, the exact mechanism behind this protection remains unclear. To better understand how Salmonella uses the O-antigen to survive in the blood, we propose a five-year study with three main goals. First, we will investigate the specific ways the O-antigen prevents Kupffer cells from capturing Salmonella. Second, we will test the potential of phage therapy, a promising alternative to antibiotics, to target and eliminate Salmonella by recognizing and attacking its O-antigen. Lastly we will explore whether vaccines or laboratory-made antibodies targeting the O-antigen can help the immune system clear Salmonella infections more effectively. This research will provide important new insights into how Salmonella avoids the immune system and persists in the bloodstream. Our findings could lead to the development of new therapies, including vaccines, antibody treatments, and phage therapy, to better combat bloodstream infections and reduce dependence on traditional antibiotics.