Staphylococcus aureus internalized by skin keratinocytes evade antibiotic killing

Arwa Al Kindi, Abdullah M. Alkahtani, Mayimuna Nalubega, Cecile El Chami, Catherine O'Neill, Peter Arkwright, Joanne Pennock

Research output: Contribution to journalArticlepeer-review

Abstract

Staphylococcus aureus causes the majority of skin and soft tissue infections. Half of patients treated for primary skin infections suffer recurrences within six 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.
Original languageEnglish
JournalFrontiers in Microbiology
Early online date24 Sept 2019
DOIs
Publication statusPublished - 2019

Keywords

  • Staphylococcus aureus
  • keratinocyte
  • Antibiotic resistance
  • Rifampicin
  • skin-immunology
  • internalization

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute

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