Monique R. Bennett, PhD
Infectious Diseases, Pediatric
Biology, Vanderbilt University, Nashville, Tennessee
Vanderbilt University, Nashville, Tennessee
S. aureus, toxins, monoclonal antibodies, LukAB
Staphylococcus aureus is a gram-positive bacterium that commonly colonizes the human nares of up to 50% of the population. It is the most common cause of invasive bacterial disease in children in the U.S and causes the majority of pediatric skin and soft tissue infections. S. aureus has become a major public health threat due to antibiotic resistance and an increasing number of failed vaccine attempts, raising the urgency for novel therapeutics. To develop new anti-staphylococcal preventive therapies, a more thorough understanding of the adaptive response to invasive S. aureus infections will be necessary. This research proposes to more effectively define the neutrophil targeting leukotoxin, LukAB, and its contribution to invasive pediatric infections. Studies have shown that LukAB is present in all clinical isolates tested to date and that children with invasive S. aureus infections mount a neutralizing, high-titer antibody response to LukAB. This indicates this toxin is important for successful S. aureus infection and recognition by the human host. In order to test this, human monoclonal antibodies (mAbs) against LukAB from pediatric human subjects with invasive S. aureus infection have been isolated, and this research aims to more fully define their diverse mechanisms of action using a combination of flow cytometric, ELISA-based, and ex vivo assays using human blood. Further understanding these processes will increase understanding of the humoral response to LukAB and its importance to S. aureus pathogenesis.