title: Theoretical and experimental evidence for eliminating persister bacteria by manipulating killing timing.
abstract: Formation of a transient sub-population of bacteria, referred to as persisters, is one of the most important and least understood mechanisms that bacteria employ to evade elimination. Persister cells appear to be slow-growing bacteria that are broadly protected from a wide range of antibiotics. Using both theoretical and experimental methods, we show that alternating the application and withdrawal of antibiotics can be an effective treatment-as long as the timing of the protocol is estimated with precision. More specifically, we demonstrate that timing the alternating treatment based on theoretical predictions is confirmed using experimental observations. These results support a large class of theoretical studies that show that, even without complete understanding of the biological mechanisms, these models can provide insight into properties of the system.
authors.affiliation: Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany cogan@math.fsu.edu.
authors.forename: N G
authors.initials: NG
authors.lastname: Cogan
authors.affiliation: Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Rath
authors.affiliation: Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kommerein
authors.affiliation: Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: S N
authors.initials: SN
authors.lastname: Stumpp
authors.affiliation: Department of Prosthetic Dentistry and Biomedical Materials Science, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stiesch
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000502:physiology*; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Staphylococcus aureus; biofilm; mathematical modeling; ofloxacin; persister; tolerance