title: Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments.
abstract: Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.|Institute of Science and Technology, Klosterneuburg 3400, Austria.
authors.forename: Remy
authors.initials: R
authors.lastname: Chait
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Palmer
authors.affiliation: Faculty of Biology, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Yelin
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.|Faculty of Biology, Technion, Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Roy
authors.initials: R
authors.lastname: Kishony
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D004352:Drug Resistance, Microbial / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013753:Tetracycline Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D004318:Doxycycline