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

Shoufeng Yang, Iain D Hay, David R Cameron, Mary Speir, Bintao Cui, Feifei Su, Anton Yariv Peleg, Trevor J Lithgow, Margaret A Deighton, Yue Qu

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

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 (MBCbiofilm). Two populations of persister cells were observed: bacteria that survived antibiotics at MBCbiofilm 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 MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.
Original languageEnglish
Article number18578
Number of pages11
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - 2015

Cite this

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title = "Antibiotic regimen based on population analysis of residing persister cells eradicates Staphylococcus epidermidis biofilms",
abstract = "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 (MBCbiofilm). Two populations of persister cells were observed: bacteria that survived antibiotics at MBCbiofilm 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 MBCbiofilm for an extended period, might eradicate S. epidermidis biofilms. Potential uses for this strategy are in antibiotic lock techniques and inhaled aerosolized antibiotics.",
author = "Shoufeng Yang and Hay, {Iain D} and Cameron, {David R} and Mary Speir and Bintao Cui and Feifei Su and Peleg, {Anton Yariv} and Lithgow, {Trevor J} and Deighton, {Margaret A} and Yue Qu",
year = "2015",
doi = "10.1038/srep18578",
language = "English",
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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 Yariv; Lithgow, Trevor J; Deighton, Margaret A; Qu, Yue.

In: Scientific Reports, Vol. 5, 18578, 2015.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Yang, Shoufeng

AU - Hay, Iain D

AU - Cameron, David R

AU - Speir, Mary

AU - Cui, Bintao

AU - Su, Feifei

AU - Peleg, Anton Yariv

AU - Lithgow, Trevor J

AU - Deighton, Margaret A

AU - Qu, Yue

PY - 2015

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AB - 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 (MBCbiofilm). Two populations of persister cells were observed: bacteria that survived antibiotics at MBCbiofilm 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 MBCbiofilm 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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