Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

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.

Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells

“…S. aureus has been known as an extracellular pathogen, but recent studies have shown that S. aureus can infect human skin epithelial cells [ 12 , 13 ]. In this study, we cocultured HaCaT cells with S. aureus for the times indicated in Figure 1 A and examined the intracellular colony forming unit (CFU) of S. aureus .…”

Phosphatidylinositol-specific phospholipase C enhances epidermal penetration by Staphylococcus aureus

“…Since PI-PLC contributes to the intracellular survival and proliferation of S. aureus in HaCaT cells, PI-PLC may protect S. aureus from AMPs and enhance epidermal penetration by supporting the intracellular persistence of S. aureus. Besides AMPs, S. aureus is able to evade antibiotic eradication by invasion and persistent colonization in cells such as keratinocytes 40 . Therefore, PI-PLC inhibition may enhance the efficiency of antibiotic treatment.…”

Isolation and identification of microorganisms in selected cosmetic products tester

“…P. acnes were one of the bacteria that caused acne observed in tester samples (Scholz and Kilian, 2016). Furthermore, S. aureus was isolated and is among the most important bacteria that cause disease in humans including skin infections and abscesses (Al Kindi et al, 2019). These symptoms could occur due to the impairment of the human immune system, skin structure, and wounded epithelium (Al Kindi et al, 2019).…”