title: Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient.
abstract: During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients.
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
authors.forename: Felix J H
authors.initials: FJ
authors.lastname: Hol
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Hubert
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Dekker
authors.affiliation: Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, The Netherlands.|Department of Ecology, Faculty of Biological Sciences, P. Catholic University of Chile, Santiago, Chile.|Institute of Physics, Faculty of Physics, P. Catholic University of Chile, Santiago, Chile.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Keymer
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology*; D018407:Bacterial Physiological Phenomena; D002465:Cell Movement / Q000502:physiology*; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents