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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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2019-09-01
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Series: | Frontiers in Microbiology |
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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. |
first_indexed | 2024-04-14T06:43:25Z |
format | Article |
id | doaj.art-e3bafa6168494283b29262d2164e4089 |
institution | Directory Open Access Journal |
issn | 1664-302X |
language | English |
last_indexed | 2024-04-14T06:43:25Z |
publishDate | 2019-09-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Microbiology |
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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