---
_id: '10812'
abstract:
- lang: eng
  text: Several promising strategies based on combining or cycling different antibiotics
    have been proposed to increase efficacy and counteract resistance evolution, but
    we still lack a deep understanding of the physiological responses and genetic
    mechanisms that underlie antibiotic interactions and the clinical applicability
    of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological
    stress responses and emerging resistance mutations (occurring at different time
    scales) generate complex and often unpredictable dynamics. In this Review, we
    present our current understanding of bacterial cell physiology and genetics of
    responses to antibiotics. We emphasize recently discovered mechanisms of synergistic
    and antagonistic drug interactions, hysteresis in temporal interactions between
    antibiotics that arise from microbial physiology and interactions between antibiotics
    and resistance mutations that can cause collateral sensitivity or cross-resistance.
    We discuss possible connections between the different phenomena and indicate relevant
    research directions. A better and more unified understanding of drug and genetic
    interactions is likely to advance antibiotic therapy.
acknowledgement: The authors thank B. Kavčič and H. Schulenburg for constructive feedback
  on the manuscript.
article_processing_charge: No
article_type: review
author:
- first_name: Roderich
  full_name: Römhild, Roderich
  id: 68E56E44-62B0-11EA-B963-444F3DDC885E
  last_name: Römhild
  orcid: 0000-0001-9480-5261
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- first_name: Dan I.
  full_name: Andersson, Dan I.
  last_name: Andersson
citation:
  ama: Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial
    responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. 2022;20:478-490.
    doi:<a href="https://doi.org/10.1038/s41579-022-00700-5">10.1038/s41579-022-00700-5</a>
  apa: Römhild, R., Bollenbach, M. T., &#38; Andersson, D. I. (2022). The physiology
    and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews
    Microbiology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41579-022-00700-5">https://doi.org/10.1038/s41579-022-00700-5</a>
  chicago: Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology
    and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews
    Microbiology</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s41579-022-00700-5">https://doi.org/10.1038/s41579-022-00700-5</a>.
  ieee: R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics
    of bacterial responses to antibiotic combinations,” <i>Nature Reviews Microbiology</i>,
    vol. 20. Springer Nature, pp. 478–490, 2022.
  ista: Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics
    of bacterial responses to antibiotic combinations. Nature Reviews Microbiology.
    20, 478–490.
  mla: Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses
    to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>, vol. 20, Springer
    Nature, 2022, pp. 478–90, doi:<a href="https://doi.org/10.1038/s41579-022-00700-5">10.1038/s41579-022-00700-5</a>.
  short: R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology
    20 (2022) 478–490.
date_created: 2022-03-04T04:33:49Z
date_published: 2022-08-01T00:00:00Z
date_updated: 2023-08-02T14:41:44Z
day: '01'
department:
- _id: CaGu
doi: 10.1038/s41579-022-00700-5
external_id:
  isi:
  - '000763891900001'
  pmid:
  - '35241807'
intvolume: '        20'
isi: 1
keyword:
- General Immunology and Microbiology
- Microbiology
- Infectious Diseases
language:
- iso: eng
month: '08'
oa_version: None
page: 478-490
pmid: 1
publication: Nature Reviews Microbiology
publication_identifier:
  eissn:
  - 1740-1534
  issn:
  - 1740-1526
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: The physiology and genetics of bacterial responses to antibiotic combinations
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 20
year: '2022'
...