Osteomyelitis is a severe bone infection frequently caused by Staphylococcus aureus. Osteomyelitis most commonly occurs when patients are exposed to S. aureus during joint replacement surgery. Antibiotics may be prescribed to treat the infection, but are often ineffective in eradicating the bacteria due to the ability of S. aureus to develop intraosteoblastic infections. The mechanism through which S. aureus causes these infections is not fully understood. Staphylococcal hemolysins are known to be involved in membrane penetration and possibly involved in development of these intracellular infections. To gain insight into intraosteoblastic S. aureus infections, we investigated two known α-hemolysin inhibitors and their effect on the quantity of internalized S. aureus over a 48-hour period. β-cyclodextrin is a known inhibitor of α-hemolysin pore formation. We found a dose dependent decrease in intracellular S. aureus in MG-63 bone cells infected with the bacteria in the presence of this inhibitor. We also tested a peptide that was predicted, using an in silico based approach, to inhibit α-hemolysin pore formation on S. aureus infected MG-63 cells. Lactate Dehydrogenase Assays showed these α-hemolytic inhibitors produce no significant adverse effects to bone cells and therefore combinational therapy that includes an α-hemolysin inhibitor and an antibiotic may be effective in preventing intraosteoblastic S. aureus infections.

Effects of alpha-hemolysin inhibitors on intraosteoblastic Staphylococcus aureus

2019 Spring National Meeting

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