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.

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.

Metrics

  • 13,712
    views
  • 1,828
    downloads
  • 124
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease
    Devon M Fitzgerald
    Insight

    The way that bacteria grow – either floating in liquid or attached to a surface – affects their ability to evolve antimicrobial resistance and our ability to treat infections.

    1. Evolutionary Biology
    2. Microbiology and Infectious Disease
    Zachary H Williams, Alvaro Dafonte Imedio ... Welkin E Johnson
    Research Article Updated

    HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact proviruses, but no replication competent HML-2 proviruses have been identified in humans. HML-2-related proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact open reading frames, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 106 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3′ long terminal repeat (LTR), derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8-derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec–RcRE export system was replaced by a CTE mechanism.