title: Sublethal streptomycin concentrations and lytic bacteriophage together promote resistance evolution.
abstract: Sub-minimum inhibiting concentrations (sub-MICs) of antibiotics frequently occur in natural environments owing to wide-spread antibiotic leakage by human action. Even though the concentrations are very low, these sub-MICs have recently been shown to alter bacterial populations by selecting for antibiotic resistance and increasing the rate of adaptive evolution. However, studies are lacking on how these effects reverberate into key ecological interactions, such as bacteria-phage interactions. Previously, co-selection of bacteria by phages and antibiotic concentrations exceeding MICs has been hypothesized to decrease the rate of resistance evolution because of fitness costs associated with resistance mutations. By contrast, here we show that sub-MICs of the antibiotic streptomycin (Sm) increased the rate of phage resistance evolution, as well as causing extinction of the phage. Notably, Sm and the phage in combination also enhanced the evolution of Sm resistance compared with Sm alone. These observations demonstrate the potential of sub-MICs of antibiotics to impact key ecological interactions in microbial communities with evolutionary outcomes that can radically differ from those associated with high concentrations. Our findings also contribute to the understanding of ecological and evolutionary factors essential for the management of the antibiotic resistance problem.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.
authors.affiliation: Department of Food and Environmental Sciences/Microbiology and Biotechnology, University of Helsinki, PO Box 65, 00014 Helsinki, Finland.
authors.forename: Johannes
authors.identifier: 0000-0003-1329-2025
authors.initials: J
authors.lastname: Cairns
authors.affiliation: Department of Evolutionary Ecology/Community Dynamics Group, Max Planck Institute for Evolutionary Biology, August Thienemann Street 2, Plön 24306, Germany.
authors.forename: Lutz
authors.identifier: 0000-0002-3885-5253
authors.initials: L
authors.lastname: Becks
authors.affiliation: Department of Biological and Environmental Science/Centre of Excellence in Biological Interactions, University of Jyväskylä, PO Box 35, 40014 Jyväskylä, Finland.
authors.forename: Matti
authors.identifier: 0000-0003-3499-5248
authors.initials: M
authors.lastname: Jalasvuori
authors.affiliation: Department of Food and Environmental Sciences/Microbiology and Biotechnology, University of Helsinki, PO Box 65, 00014 Helsinki, Finland teppo.hiltunen@helsinki.fi.
authors.forename: Teppo
authors.identifier: 0000-0001-7206-2399
authors.initials: T
authors.lastname: Hiltunen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005075:Biological Evolution; D019143:Evolution, Molecular; D017105:Pseudomonas Phages / Q000502:physiology*; D011551:Pseudomonas fluorescens / Q000187:drug effects / Q000235:genetics* / Q000821:virology*; D013307:Streptomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013307:Streptomycin
keywords: Pseudomonas fluorescens; antibiotic resistance; experimental evolution; phage resistance; phage Φ2; sublethal antibiotic concentrations