Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide

The rise in antimicrobial resistant bacteria have prompted the need for antibiotic alternatives. To address this problem, significant attention has been given to the antimicrobial use and novel applications of copper. As novel applications of antimicrobial copper increase, it is important to investi...

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Main Authors: Sada M. Boyd, Kristen L. Rhinehardt, Akamu J. Ewunkem, Scott H. Harrison, Misty D. Thomas, Joseph L. Graves
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/11/6/711
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author Sada M. Boyd
Kristen L. Rhinehardt
Akamu J. Ewunkem
Scott H. Harrison
Misty D. Thomas
Joseph L. Graves
author_facet Sada M. Boyd
Kristen L. Rhinehardt
Akamu J. Ewunkem
Scott H. Harrison
Misty D. Thomas
Joseph L. Graves
author_sort Sada M. Boyd
collection DOAJ
description The rise in antimicrobial resistant bacteria have prompted the need for antibiotic alternatives. To address this problem, significant attention has been given to the antimicrobial use and novel applications of copper. As novel applications of antimicrobial copper increase, it is important to investigate how bacteria may adapt to copper over time. Here, we used experimental evolution with re-sequencing (EER-seq) and RNA-sequencing to study the evolution of copper resistance in <i>Escherichia coli</i>. Subsequently, we tested whether copper resistance led to rifampicin, chloramphenicol, bacitracin, and/or sulfonamide resistance. Our results demonstrate that <i>E. coli</i> is capable of rapidly evolving resistance to CuSO<sub>4</sub> after 37 days of selection. We also identified multiple de novo mutations and differential gene expression patterns associated with copper, most notably those mutations identified in the <i>cpx</i> gene. Furthermore, we found that the copper resistant bacteria had decreased sensitivity when compared to the ancestors in the presence of chloramphenicol, bacitracin, and sulfonamide. Our data suggest that the selection of copper resistance may inhibit growth in the antimicrobials tested, resulting in evolutionary trade-offs. The results of our study may have important implications as we consider the antimicrobial use of copper and how bacteria may respond to increased use over time.
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spelling doaj.art-1c8ecd5c527b439294d0230a8b8789cf2023-11-23T15:15:59ZengMDPI AGAntibiotics2079-63822022-05-0111671110.3390/antibiotics11060711Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and SulfonamideSada M. Boyd0Kristen L. Rhinehardt1Akamu J. Ewunkem2Scott H. Harrison3Misty D. Thomas4Joseph L. Graves5Department of Ecology and Evolutionary Biology, University of California, 612 Charles E. Young Drive South, Los Angeles, CA 90095, USADepartment of Computational Data Science and Engineering, North Carolina Agricultural and Technical State University, 1601 E. Market Street, Greensboro, NC 27411, USADepartment of Biological Sciences, Winston Salem State University, 601 S. Martin Luther King Jr. Drive, Win-ston-Salem, NC 27110, USADepartment of Biology, North Carolina Agricultural and Technical State University, 1601 E. Market Street, Greensboro, NC 27411, USADepartment of Biology, North Carolina Agricultural and Technical State University, 1601 E. Market Street, Greensboro, NC 27411, USADepartment of Biology, North Carolina Agricultural and Technical State University, 1601 E. Market Street, Greensboro, NC 27411, USAThe rise in antimicrobial resistant bacteria have prompted the need for antibiotic alternatives. To address this problem, significant attention has been given to the antimicrobial use and novel applications of copper. As novel applications of antimicrobial copper increase, it is important to investigate how bacteria may adapt to copper over time. Here, we used experimental evolution with re-sequencing (EER-seq) and RNA-sequencing to study the evolution of copper resistance in <i>Escherichia coli</i>. Subsequently, we tested whether copper resistance led to rifampicin, chloramphenicol, bacitracin, and/or sulfonamide resistance. Our results demonstrate that <i>E. coli</i> is capable of rapidly evolving resistance to CuSO<sub>4</sub> after 37 days of selection. We also identified multiple de novo mutations and differential gene expression patterns associated with copper, most notably those mutations identified in the <i>cpx</i> gene. Furthermore, we found that the copper resistant bacteria had decreased sensitivity when compared to the ancestors in the presence of chloramphenicol, bacitracin, and sulfonamide. Our data suggest that the selection of copper resistance may inhibit growth in the antimicrobials tested, resulting in evolutionary trade-offs. The results of our study may have important implications as we consider the antimicrobial use of copper and how bacteria may respond to increased use over time.https://www.mdpi.com/2079-6382/11/6/711<i>Escherichia coli</i>copperexperimental evolutiongenomicsantibiotics
spellingShingle Sada M. Boyd
Kristen L. Rhinehardt
Akamu J. Ewunkem
Scott H. Harrison
Misty D. Thomas
Joseph L. Graves
Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
Antibiotics
<i>Escherichia coli</i>
copper
experimental evolution
genomics
antibiotics
title Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
title_full Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
title_fullStr Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
title_full_unstemmed Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
title_short Experimental Evolution of Copper Resistance in <i>Escherichia coli</i> Produces Evolutionary Trade-Offs in the Antibiotics Chloramphenicol, Bacitracin, and Sulfonamide
title_sort experimental evolution of copper resistance in i escherichia coli i produces evolutionary trade offs in the antibiotics chloramphenicol bacitracin and sulfonamide
topic <i>Escherichia coli</i>
copper
experimental evolution
genomics
antibiotics
url https://www.mdpi.com/2079-6382/11/6/711
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