Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants
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 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02001/full |
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| author | Alasdair T. M. Hubbard Alasdair T. M. Hubbard Nazila V. Jafari Nicholas Feasey Nicholas Feasey Jennifer L. Rohn Adam P. Roberts Adam P. Roberts |
| author_facet | Alasdair T. M. Hubbard Alasdair T. M. Hubbard Nazila V. Jafari Nicholas Feasey Nicholas Feasey Jennifer L. Rohn Adam P. Roberts Adam P. Roberts |
| author_sort | Alasdair T. M. Hubbard |
| collection | DOAJ |
| description | 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 utilized 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-h 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 preliminary study highlights the risks in relying on a single culture protocol as a model system to predict the behavior 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. |
| first_indexed | 2024-12-20T02:35:44Z |
| format | Article |
| id | doaj.art-e4c405229015412b88cfedff55e147db |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-20T02:35:44Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-e4c405229015412b88cfedff55e147db2022-12-21T19:56:27ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-08-011010.3389/fmicb.2019.02001469512Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli MutantsAlasdair T. M. Hubbard0Alasdair T. M. Hubbard1Nazila V. Jafari2Nicholas Feasey3Nicholas Feasey4Jennifer L. Rohn5Adam P. Roberts6Adam P. Roberts7Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United KingdomCentre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United KingdomCentre for Urological Biology, Department of Renal Medicine, University College London, London, United KingdomDepartment of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United KingdomMalawi-Liverpool-Wellcome Trust Clinical Research Programme, University of Malawi, College of Medicine, Blantyre, MalawiCentre for Urological Biology, Department of Renal Medicine, University College London, London, United KingdomDepartment of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United KingdomCentre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, United KingdomThe 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 utilized 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-h 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 preliminary study highlights the risks in relying on a single culture protocol as a model system to predict the behavior 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.https://www.frontiersin.org/article/10.3389/fmicb.2019.02001/fullevolutionantibiotic resistancefitnessbiological costurethral organoidurine |
| spellingShingle | Alasdair T. M. Hubbard Alasdair T. M. Hubbard Nazila V. Jafari Nicholas Feasey Nicholas Feasey Jennifer L. Rohn Adam P. Roberts Adam P. Roberts Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants Frontiers in Microbiology evolution antibiotic resistance fitness biological cost urethral organoid urine |
| title | Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants |
| title_full | Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants |
| title_fullStr | Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants |
| title_full_unstemmed | Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants |
| title_short | Effect of Environment on the Evolutionary Trajectories and Growth Characteristics of Antibiotic-Resistant Escherichia coli Mutants |
| title_sort | effect of environment on the evolutionary trajectories and growth characteristics of antibiotic resistant escherichia coli mutants |
| topic | evolution antibiotic resistance fitness biological cost urethral organoid urine |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02001/full |
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