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.
authors.affiliation: Department of Infectious diseases, Wenzhou Central Hospital, Zhejiang, China 325000.|Dingli College of Clinical Medicine, Wenzhou Medical University, Zhejiang, China 325000.
authors.forename: Shoufeng
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Microbiology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.
authors.forename: Iain D
authors.initials: ID
authors.lastname: Hay
authors.affiliation: Department of Microbiology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.
authors.forename: David R
authors.initials: DR
authors.lastname: Cameron
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Speir
authors.affiliation: School of Applied Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia.
authors.forename: Bintao
authors.initials: B
authors.lastname: Cui
authors.affiliation: Department of Infectious diseases, Wenzhou Central Hospital, Zhejiang, China 325000.|Dingli College of Clinical Medicine, Wenzhou Medical University, Zhejiang, China 325000.
authors.forename: Feifei
authors.initials: F
authors.lastname: Su
authors.affiliation: Department of Microbiology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.|Department of Infectious Diseases, The Alfred Hospital, Melbourne 3004, Victoria, Australia.
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Peleg
authors.affiliation: Department of Microbiology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
authors.affiliation: School of Applied Sciences, RMIT University, Plenty Road, Bundoora 3083, Victoria, Australia.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Deighton
authors.affiliation: Department of Microbiology, School of Medicine, Nursing and Health Sciences, Monash University, Clayton 3800, Victoria, Australia.|Department of Infectious Diseases, The Alfred Hospital, Melbourne 3004, Victoria, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D055499:Catheter-Related Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity
chemical_list: D000900:Anti-Bacterial Agents