2349. Elucidating the Pathogenesis of <i>Staphylococcus aureus</i> During Hyperglycemic Osteomyelitis

Abstract Background Staphylococcus aureus is a leading cause of antibiotic-resistant bacterial infections and can infect nearly every organ the human body. One common manifestation S. disease invasive bone infection, or osteomyelitis. Osteomyelitis one most difficult to treat infections, often necessitating prolonged antibiotic treatment surgical interventions. Hyperglycemia, elevated blood glucose concentration, increases risk for developing We hypothesized that adapts specifically altered host environment during hyperglycemic osteomyelitis, thereby contributing increased infection severity. Methods To model we treated mice with streptozotocin prior in post-traumatic osteomyelitis model. analyzed burdens homogenized tissues parameters microcomputed tomography. identify changes spatial molecular architecture infected, femurs, utilized imaging mass spectrometry. Finally, obtain comprehensive understanding metabolic virulence genes essential staphylococcal growth vivo mice, performed transposon sequencing experiment. Results discovered sustained within infected femurs greater dissemination other organs. also found experienced rates destruction loss trabecular volume, suggesting hyperglycemia exacerbates infection-associated loss. identified 71 as uniquely compared euglycemic infection. Conclusion Hyperglycemia results Multiple involved metabolism roles fitness acidic environments were comorbid By identifying survival have potential inform targeted therapeutic development exacerbated patients hyperglycemia. Disclosures All Authors: No reported disclosures.