Grant: Travel Awards - Institute Community Support

Staphylococcus aureus is a bacterium that can cause severe diseases, including life-threatening bloodstream infections. A major concern is that these infections are becoming harder to treat because the bacteria can resist antibiotics and evade the immune system. One way S. aureus does this is by releasing toxins known as superantigens (SAgs). These toxins push the immune system into overdrive, causing an excessive release of a molecule called interferon gamma (IFNg). Under normal conditions, IFNg helps fight infections. However, our research shows that when IFNg levels get too high-especially due to the action of SAgs-it can actually help the bacteria survive. Specifically, S. aureus takes advantage of changes in immune cells called macrophages, which are meant to kill bacteria. High IFNg levels alter how these cells recycle and process materials inside themselves, unintentionally giving S. aureus access to nutrients it needs to grow. We developed new lab tests to measure how well S. aureus grows inside these immune cells when IFNg is elevated. We also explored ways to block the pathways that the bacteria hijack, and found that doing so reduced bacterial growth. These findings were tested not only in the lab, but also in animal models to confirm their relevance during actual infection. Finally, we began testing new protein-based treatments that might interfere with this bacterial strategy. By targeting the IFNg-driven changes in macrophages, we aim to develop new therapies to fight S. aureus infections, especially those that don't respond well to current antibiotics.