Abstract
Staphylococcus aureus
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
S. aureus
internalized by human skin keratinocytes are effectively eradicated by standard anti-staphylococcal antibiotics.
S. aureus
, but not
S. epidermidis
, 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
S. aureus
, even at 20-fold their standard minimal inhibitory concentration. We conclude that internalization of
S. aureus
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
S. aureus
are to be effectively eradicated and recurrent infections prevented.