Aimee (Wilde) Potter
Staphylococcus aureus is a widespread human pathogen, capable of infecting nearly every organ in the human body. S. aureus is particularly adept at colonizing bone to cause osteomyelitis. In order to discover the genetic programs that accommodate bacterial survival in the skeletal environment, we used an unbiased, genome-wide approach known as transposon sequencing (TnSeq), which identified the S. aureus two-component system SrrAB as essential for sustaining invasive osteomyelitis. SrrAB is known to regulate the aerobic/anaerobic shift and modulate toxin production. These characteristics are especially important in bone, which is an intrinsically hypoxic tissue and is sensitive to pathogen-induced bone destruction. Intriguingly, preliminary data indicate that SrrAB also regulates nutrient utilization programs. The ability of SrrAB to modulate nutrient utilization may be particularly important during osteomyelitis, as resident bone-forming osteoblasts and bone-resorbing osteoclasts exhibit a specialized metabolism requiring elevated glucose uptake, thereby limiting carbon availability to S. aureus during osteomyelitis. Accordingly, this research investigates SrrAB-dependent virulence responses and metabolic adaptations to the hypoxic skeletal environment.
Cohort: 2014
Principal Investigator: James E. Cassat, M.D., Ph.D.
Internship Company: MedImmune
Internship Year: 2017
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