Hiding in plain sight: How Staphylococcus aureus evades antibiotic treatment in the skin

Activity: Talk or presentationOral presentationResearch

Description

Background. Staphylococcus aureus is the most common cause of skin and soft tissue infections. 40 – 50% of patients treated for primary infections suffer recurrences within six months. We hypothesized that internalization of S. aureus by human keratinocytes provides a niche for bacteria to escape killing by antibiotics, and may provide a reservoir for recurrent infection.
Methods. Internalization of S. aureus by human keratinocytes was studied by flow cytometry and microscopy. Viability of internalized S. aureus was assessed, as was the bactericidal potential of anti-staphylococcal antibiotics routinely used in clinical practice, as well as after blocking bacterial uptake with anti-integrin antibodies and inhibitors of actin polymerization.
Results. Primary human keratinocytes readily internalized clinical and lab strains of S. aureus but not S. epidermidis. S. aureus survived inside the skin cells for 24 hours without inducing any cytotoxicity or release of IL-33. Cytochalasin D, anti-Rac1 and anti-a1b5 integrin antibodies all suppressed internalization of the bacteria. Physical lysis of keratinocytes haboring S. aureus resulted in the release of viable, proliferating bacteria. Flucloxacillin, teicoplanin, clindamycin and linezolid, which had Minimum Inhibitory Concentrations (MIC) of 0.1 to 2.0 ug/ml for extracellular bacteria did not effectively kill the internalized S. aureus, even at 20-fold the MIC concentration. Rifampicin was the only antibiotic that had similar bactericidal potential for extra-cellular and internalized S. aureus. New bactericidal agents are urgently needed which target internalized S aureus and prevent recurrent infection.

Period20 Jun 2019
Event title3rd Caparica Conference Antibiotic Resistance 2019
Event typeConference
LocationCaparica, PortugalShow on map
Degree of RecognitionInternational

Keywords

  • antibiotics
  • resistance
  • Infection
  • bacteria
  • dermatology