Understanding How Starvation Shapes Infection

Bacterial pathogens are threats to human health due to antibiotic resistance and the failure of antibiotics to eradicate antibiotic sensitive strains during infection. This threat is exemplified by Staphylococcus aureus, which is a leading cause of bone and joint infections, as well as skin and soft tissue infections. To combat invading pathogens, the immune response restricts the availability of essential nutrients at sites of infection a defense known as “nutritional immunity”. The restriction of essential metals by the immune response sensitizes S. aureus to the oxidative burst of phagocytes and other host-defenses, yet it remains a deadly pathogen. Conversely, metal starvation decreases efficacy of b-lactam antibiotics, a first-line treatment for many bacterial infections. Research in the Kehl-Fie laboratory seeks to understand how nutritional immunity impacts invaders, altering their sensitivity to host-defenses and antibiotics, and to determine the adaptations that enable pathogens to overcome host-imposed starvation.