AUTHOR=Al Kindi Arwa , Alkahtani Abdullah M. , Nalubega Mayimuna , El-Chami Cecile , O’Neill Catherine , Arkwright Peter D. , Pennock Joanne L. 

TITLE=Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02242

DOI=10.3389/fmicb.2019.02242

ISSN=1664-302X

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