Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

Abstract

<i>Staphylococcus aureus</i> causes the majority of skin and soft tissue infections. Half of patients treated for primary skin infections suffer recurrences within 6 months despite appropriate antibiotic sensitivities and infection control measures. We investigated whether <i>S. aureus</i> internalized by human skin keratinocytes are effectively eradicated by standard anti-staphylococcal antibiotics. <i>S. aureus</i>, but not <i>S. epidermidis</i>, were internalized and survive within keratinocytes without inducing cytotoxicity or releasing the IL-33 danger signal. Except for rifampicin, anti-staphylococcal antibiotics in regular clinical use, including flucloxacillin, teicoplanin, clindamycin, and linezolid, did not kill internalized <i>S. aureus</i>, even at 20-fold their standard minimal inhibitory concentration. We conclude that internalization of <i>S. aureus</i> by human skin keratinocytes allows the bacteria to evade killing by most anti-staphylococcal antibiotics. Antimicrobial strategies, including antibiotic combinations better able to penetrate into mammalian cells are required if intracellular <i>S. aureus</i> are to be effectively eradicated and recurrent infections prevented.