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Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms

Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establi...

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Autores principales: Yang, Shoufeng, Hay, Iain D., Cameron, David R., Speir, Mary, Cui, Bintao, Su, Feifei, Peleg, Anton Y., Lithgow, Trevor, Deighton, Margaret A., Qu, Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685274/
https://www.ncbi.nlm.nih.gov/pubmed/26687035
http://dx.doi.org/10.1038/srep18578
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author Yang, Shoufeng
Hay, Iain D.
Cameron, David R.
Speir, Mary
Cui, Bintao
Su, Feifei
Peleg, Anton Y.
Lithgow, Trevor
Deighton, Margaret A.
Qu, Yue
author_facet Yang, Shoufeng
Hay, Iain D.
Cameron, David R.
Speir, Mary
Cui, Bintao
Su, Feifei
Peleg, Anton Y.
Lithgow, Trevor
Deighton, Margaret A.
Qu, Yue
author_sort Yang, Shoufeng
collection PubMed
description Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBC(biofilm)). Two populations of “persister cells” were observed: bacteria that survived antibiotics at MBC(biofilm) for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBC(biofilm) for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.
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spelling pubmed-46852742015-12-30 Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms Yang, Shoufeng Hay, Iain D. Cameron, David R. Speir, Mary Cui, Bintao Su, Feifei Peleg, Anton Y. Lithgow, Trevor Deighton, Margaret A. Qu, Yue Sci Rep Article Biofilm formation is a major pathogenicity strategy of Staphylococcus epidermidis causing various medical-device infections. Persister cells have been implicated in treatment failure of such infections. We sought to profile bacterial subpopulations residing in S. epidermidis biofilms, and to establish persister-targeting treatment strategies to eradicate biofilms. Population analysis was performed by challenging single biofilm cells with antibiotics at increasing concentrations ranging from planktonic minimum bactericidal concentrations (MBCs) to biofilm MBCs (MBC(biofilm)). Two populations of “persister cells” were observed: bacteria that survived antibiotics at MBC(biofilm) for 24/48 hours were referred to as dormant cells; those selected with antibiotics at 8 X MICs for 3 hours (excluding dormant cells) were defined as tolerant-but-killable (TBK) cells. Antibiotic regimens targeting dormant cells were tested in vitro for their efficacies in eradicating persister cells and intact biofilms. This study confirmed that there are at least three subpopulations within a S. epidermidis biofilm: normal cells, dormant cells, and TBK cells. Biofilms comprise more TBK cells and dormant cells than their log-planktonic counterparts. Using antibiotic regimens targeting dormant cells, i.e. effective antibiotics at MBC(biofilm) for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics. Nature Publishing Group 2015-12-21 /pmc/articles/PMC4685274/ /pubmed/26687035 http://dx.doi.org/10.1038/srep18578 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Yang, Shoufeng
Hay, Iain D.
Cameron, David R.
Speir, Mary
Cui, Bintao
Su, Feifei
Peleg, Anton Y.
Lithgow, Trevor
Deighton, Margaret A.
Qu, Yue
Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title_full Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title_fullStr Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title_full_unstemmed Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title_short Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms
title_sort antibiotic regimen based on population analysis of residing persister cells eradicates staphylococcus epidermidis biofilms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685274/
https://www.ncbi.nlm.nih.gov/pubmed/26687035
http://dx.doi.org/10.1038/srep18578
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