title: Collective antibiotic tolerance: mechanisms, dynamics and intervention.
abstract: Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. Also important, however, is the fact that a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming and interpopulation interactions. These strategies can enable rapid population recovery after antibiotic treatment and provide a time window during which otherwise susceptible bacteria can acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
authors.forename: Hannah R
authors.initials: HR
authors.lastname: Meredith
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
authors.forename: Jaydeep K
authors.initials: JK
authors.lastname: Srimani
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Lopatkin
authors.affiliation: 1] Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA. [2] Center for Systems Biology, Duke University, Durham, North Carolina, USA. [3] Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA.
authors.forename: Lingchong
authors.initials: L
authors.lastname: You
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology*; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents