Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle

Abstract

Bacterial populations vary in their stress tolerance and population structure depending upon whether growth occurs in well-mixed or structured environments. We hypothesized that evolution in biofilms would generate greater genetic diversity than well-mixed environments and lead to different pathways of antibiotic resistance. We used experimental evolution and whole genome sequencing to test how the biofilm lifestyle influenced the rate, genetic mechanisms, and pleiotropic effects of resistance to ciprofloxacin in Acinetobacter baumannii populations. Both evolutionary dynamics and the identities of mutations differed between lifestyle. Planktonic populations experienced selective sweeps of mutations including the primary topoisomerase drug targets, whereas biofilm-adapted populations acquired mutations in regulators of efflux pumps. An overall trade-off between fitness and resistance level emerged, wherein biofilm-adapted clones were less resistant than planktonic but more fit in the absence of drug. However, biofilm populations developed collateral sensitivity to cephalosporins, demonstrating the clinical relevance of lifestyle on the evolution of resistance.

Data availability

Sequencing data were deposited to NCBI as Bioproject 485123.R code for filtering and data processing can be found here:https://github.com/sirmicrobe/U01_allele_freq_code.

The following data sets were generated

Article and author information

Author details

  1. Alfonso Santos-Lopez

    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9163-9947
  2. Christopher W Marshall

    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Michelle R Scribner

    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel J Snyder

    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vaughn S Cooper

    Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, United States
    For correspondence
    vaughn.cooper@pitt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7726-0765

Funding

National Institutes of Health (U01AI124302-01)

  • Vaughn S Cooper

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Version history

  1. Received: April 11, 2019
  2. Accepted: September 13, 2019
  3. Accepted Manuscript published: September 13, 2019 (version 1)
  4. Version of Record published: October 25, 2019 (version 2)

Copyright

© 2019, Santos-Lopez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alfonso Santos-Lopez
  2. Christopher W Marshall
  3. Michelle R Scribner
  4. Daniel J Snyder
  5. Vaughn S Cooper
(2019)
Evolutionary pathways to antibiotic resistance are dependent upon environmental structure and bacterial lifestyle
eLife 8:e47612.
https://doi.org/10.7554/eLife.47612

Share this article

https://doi.org/10.7554/eLife.47612

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