Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing

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 s...

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Main Authors: Arwa Al Kindi, Abdullah M. Alkahtani, Mayimuna Nalubega, Cecile El-Chami, Catherine O’Neill, Peter D. Arkwright, Joanne L. Pennock
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-09-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.02242/full
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author Arwa Al Kindi
Arwa Al Kindi
Abdullah M. Alkahtani
Mayimuna Nalubega
Mayimuna Nalubega
Cecile El-Chami
Catherine O’Neill
Peter D. Arkwright
Peter D. Arkwright
Joanne L. Pennock
Joanne L. Pennock
author_facet Arwa Al Kindi
Arwa Al Kindi
Abdullah M. Alkahtani
Mayimuna Nalubega
Mayimuna Nalubega
Cecile El-Chami
Catherine O’Neill
Peter D. Arkwright
Peter D. Arkwright
Joanne L. Pennock
Joanne L. Pennock
author_sort Arwa Al Kindi
collection DOAJ
description 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.
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spelling doaj.art-e3bafa6168494283b29262d2164e40892022-12-22T02:07:15ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-09-011010.3389/fmicb.2019.02242481150Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic KillingArwa Al Kindi0Arwa Al Kindi1Abdullah M. Alkahtani2Mayimuna Nalubega3Mayimuna Nalubega4Cecile El-Chami5Catherine O’Neill6Peter D. Arkwright7Peter D. Arkwright8Joanne L. Pennock9Joanne L. Pennock10Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United KingdomDivision of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United KingdomCollege of Medicine, King Khalid University, Abha, Saudi ArabiaLydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United KingdomDivision of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United KingdomDivision of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United KingdomDivision of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester, United KingdomLydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United KingdomDivision of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United KingdomLydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United KingdomDivision of Infection, Immunity and Respiratory Medicine, The University of Manchester, Manchester, United KingdomStaphylococcus 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.https://www.frontiersin.org/article/10.3389/fmicb.2019.02242/fullStaphylococcus aureusskinkeratinocyteinternalizationantibiotic sensitivityrifampicin
spellingShingle Arwa Al Kindi
Arwa Al Kindi
Abdullah M. Alkahtani
Mayimuna Nalubega
Mayimuna Nalubega
Cecile El-Chami
Catherine O’Neill
Peter D. Arkwright
Peter D. Arkwright
Joanne L. Pennock
Joanne L. Pennock
Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
Frontiers in Microbiology
Staphylococcus aureus
skin
keratinocyte
internalization
antibiotic sensitivity
rifampicin
title Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
title_full Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
title_fullStr Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
title_full_unstemmed Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
title_short Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing
title_sort staphylococcus aureus internalized by skin keratinocytes evade antibiotic killing
topic Staphylococcus aureus
skin
keratinocyte
internalization
antibiotic sensitivity
rifampicin
url https://www.frontiersin.org/article/10.3389/fmicb.2019.02242/full
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