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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02001

Effect of environment on the evolutionary trajectories and growth characteristics of antibiotic- resistant Escherichia coli mutants

  • 1Tropicial Disease Biology, Liverpool School of Tropical Medicine, United Kingdom
  • 2Centre for Urological Biology, University College London, United Kingdom
  • 3Department of Clinical Sciences, Liverpool School of Tropical Medicine, United Kingdom
  • 4Liverpool School of Tropical Medicine, United Kingdom

The fitness cost to bacteria of acquisition of resistance determinants is critically under-investigated, and the identification and exploitation of these fitness costs may lead to novel therapeutic strategies that prevent the emergence of antimicrobial resistance. Here we used Escherichia coli and amoxicillin-clavulanic acid (AMC) resistance as a model to understand how the artificial environments utilised in studies of bacterial fitness could affect the emergence of resistance and associated fitness costs. Further, we explored the predictive value of this data when strains were grown in the more physiologically relevant environments of urine and urothelial organoids. Resistant E. coli isolates were selected for following 24-hour exposure to sub-inhibitory concentrations of AMC in either M9, ISO or LB, followed by growth on LB agar containing AMC. No resistant colonies emerged following growth in M9, whereas resistant isolates were detected from cultures grown in ISO and LB. We observed both within and between media-type variability in the levels of resistance and fitness of the resistant mutants grown in LB. MICs and fitness of these resistant strains in different media (M9, ISO, LB, human urine and urothelial organoids) showed considerable variation. Media can therefore have a direct effect on the isolation of mutants that confer resistance to AMC and these mutants can exhibit unpredictable MIC and fitness profiles under different growth conditions. This study highlights the risks in relying on a single culture protocol as a model system to predict the behaviour and treatment response of bacteria in vivo and highlights the importance of developing comprehensive experimental designs to ensure effective translation of diagnostic procedures to successful clinical outcomes.

Keywords: evolution, antibiotic resistance, fitness, Biological cost, urethral organoid, Urine

Received: 01 May 2019; Accepted: 15 Aug 2019.

Edited by:

Henrietta Venter, University of South Australia, Australia

Reviewed by:

Isabel Gordo, Gulbenkian Institute of Science, Portugal
Marco Rinaldo Oggioni, University of Leicester, United Kingdom  

Copyright: © 2019 Hubbard, Jafari, Feasey, Rohn and Roberts. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Alasdair T. Hubbard, Liverpool School of Tropical Medicine, Tropicial Disease Biology, Liverpool, United Kingdom, alasdair.hubbard@lstmed.ac.uk
Dr. Adam P. Roberts, Liverpool School of Tropical Medicine, Liverpool, United Kingdom, adam.roberts@lstmed.ac.uk