---
_id: '8037'
abstract:
- lang: eng
  text: 'Genetic perturbations that affect bacterial resistance to antibiotics have
    been characterized genome-wide, but how do such perturbations interact with subsequent
    evolutionary adaptation to the drug? Here, we show that strong epistasis between
    resistance mutations and systematically identified genes can be exploited to control
    spontaneous resistance evolution. We evolved hundreds of Escherichia coli K-12
    mutant populations in parallel, using a robotic platform that tightly controls
    population size and selection pressure. We find a global diminishing-returns epistasis
    pattern: strains that are initially more sensitive generally undergo larger resistance
    gains. However, some gene deletion strains deviate from this general trend and
    curtail the evolvability of resistance, including deletions of genes for membrane
    transport, LPS biosynthesis, and chaperones. Deletions of efflux pump genes force
    evolution on inferior mutational paths, not explored in the wild type, and some
    of these essentially block resistance evolution. This effect is due to strong
    negative epistasis with resistance mutations. The identified genes and cellular
    functions provide potential targets for development of adjuvants that may block
    spontaneous resistance evolution when combined with antibiotics.'
article_number: '3105'
article_processing_charge: No
article_type: original
author:
- first_name: Marta
  full_name: Lukacisinova, Marta
  id: 4342E402-F248-11E8-B48F-1D18A9856A87
  last_name: Lukacisinova
  orcid: 0000-0002-2519-8004
- first_name: Booshini
  full_name: Fernando, Booshini
  last_name: Fernando
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Lukacisinova M, Fernando B, Bollenbach MT. Highly parallel lab evolution reveals
    that epistasis can curb the evolution of antibiotic resistance. <i>Nature Communications</i>.
    2020;11. doi:<a href="https://doi.org/10.1038/s41467-020-16932-z">10.1038/s41467-020-16932-z</a>
  apa: Lukacisinova, M., Fernando, B., &#38; Bollenbach, M. T. (2020). Highly parallel
    lab evolution reveals that epistasis can curb the evolution of antibiotic resistance.
    <i>Nature Communications</i>. Springer Nature. <a href="https://doi.org/10.1038/s41467-020-16932-z">https://doi.org/10.1038/s41467-020-16932-z</a>
  chicago: Lukacisinova, Marta, Booshini Fernando, and Mark Tobias Bollenbach. “Highly
    Parallel Lab Evolution Reveals That Epistasis Can Curb the Evolution of Antibiotic
    Resistance.” <i>Nature Communications</i>. Springer Nature, 2020. <a href="https://doi.org/10.1038/s41467-020-16932-z">https://doi.org/10.1038/s41467-020-16932-z</a>.
  ieee: M. Lukacisinova, B. Fernando, and M. T. Bollenbach, “Highly parallel lab evolution
    reveals that epistasis can curb the evolution of antibiotic resistance,” <i>Nature
    Communications</i>, vol. 11. Springer Nature, 2020.
  ista: Lukacisinova M, Fernando B, Bollenbach MT. 2020. Highly parallel lab evolution
    reveals that epistasis can curb the evolution of antibiotic resistance. Nature
    Communications. 11, 3105.
  mla: Lukacisinova, Marta, et al. “Highly Parallel Lab Evolution Reveals That Epistasis
    Can Curb the Evolution of Antibiotic Resistance.” <i>Nature Communications</i>,
    vol. 11, 3105, Springer Nature, 2020, doi:<a href="https://doi.org/10.1038/s41467-020-16932-z">10.1038/s41467-020-16932-z</a>.
  short: M. Lukacisinova, B. Fernando, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-06-29T07:59:35Z
date_published: 2020-06-19T00:00:00Z
date_updated: 2025-04-15T08:09:37Z
day: '19'
ddc:
- '570'
doi: 10.1038/s41467-020-16932-z
extern: '1'
external_id:
  isi:
  - '000545685100002'
  pmid:
  - '32561723'
file:
- access_level: open_access
  checksum: 4f5f49d63add331d5eb8a2bae477b396
  content_type: application/pdf
  creator: cziletti
  date_created: 2020-06-30T09:58:50Z
  date_updated: 2020-07-14T12:48:08Z
  file_id: '8071'
  file_name: 2020_NatureComm_Lukacisinova.pdf
  file_size: 1546491
  relation: main_file
file_date_updated: 2020-07-14T12:48:08Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
  grant_number: RGP0042/2013
  name: Revealing the fundamental limits of cell growth
publication: Nature Communications
publication_identifier:
  eissn:
  - '20411723'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Highly parallel lab evolution reveals that epistasis can curb the evolution
  of antibiotic resistance
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...