---
_id: '19'
abstract:
- lang: eng
  text: Bacteria regulate genes to survive antibiotic stress, but regulation can be
    far from perfect. When regulation is not optimal, mutations that change gene expression
    can contribute to antibiotic resistance. It is not systematically understood to
    what extent natural gene regulation is or is not optimal for distinct antibiotics,
    and how changes in expression of specific genes quantitatively affect antibiotic
    resistance. Here we discover a simple quantitative relation between fitness, gene
    expression, and antibiotic potency, which rationalizes our observation that a
    multitude of genes and even innate antibiotic defense mechanisms have expression
    that is critically nonoptimal under antibiotic treatment. First, we developed
    a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression
    and knockout libraries, finding that resistance to a range of 31 antibiotics could
    result from changing expression of a large and functionally diverse set of genes,
    in a primarily but not exclusively drug-specific manner. Second, by synthetically
    controlling the expression of single-drug and multidrug resistance genes, we observed
    that their fitness-expression functions changed dramatically under antibiotic
    treatment in accordance with a log-sensitivity relation. Thus, because many genes
    are nonoptimally expressed under antibiotic treatment, many regulatory mutations
    can contribute to resistance by altering expression and by activating latent defenses.
article_processing_charge: No
article_type: original
author:
- first_name: Adam
  full_name: Palmer, Adam
  last_name: Palmer
- first_name: Remy P
  full_name: Chait, Remy P
  id: 3464AE84-F248-11E8-B48F-1D18A9856A87
  last_name: Chait
  orcid: 0000-0003-0876-3187
- first_name: Roy
  full_name: Kishony, Roy
  last_name: Kishony
citation:
  ama: Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential
    for antibiotic resistance. <i>Molecular Biology and Evolution</i>. 2018;35(11):2669-2684.
    doi:<a href="https://doi.org/10.1093/molbev/msy163">10.1093/molbev/msy163</a>
  apa: Palmer, A., Chait, R. P., &#38; Kishony, R. (2018). Nonoptimal gene expression
    creates latent potential for antibiotic resistance. <i>Molecular Biology and Evolution</i>.
    Oxford University Press. <a href="https://doi.org/10.1093/molbev/msy163">https://doi.org/10.1093/molbev/msy163</a>
  chicago: Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression
    Creates Latent Potential for Antibiotic Resistance.” <i>Molecular Biology and
    Evolution</i>. Oxford University Press, 2018. <a href="https://doi.org/10.1093/molbev/msy163">https://doi.org/10.1093/molbev/msy163</a>.
  ieee: A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates
    latent potential for antibiotic resistance,” <i>Molecular Biology and Evolution</i>,
    vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018.
  ista: Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent
    potential for antibiotic resistance. Molecular Biology and Evolution. 35(11),
    2669–2684.
  mla: Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for
    Antibiotic Resistance.” <i>Molecular Biology and Evolution</i>, vol. 35, no. 11,
    Oxford University Press, 2018, pp. 2669–84, doi:<a href="https://doi.org/10.1093/molbev/msy163">10.1093/molbev/msy163</a>.
  short: A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018)
    2669–2684.
date_created: 2018-12-11T11:44:11Z
date_published: 2018-08-28T00:00:00Z
date_updated: 2023-10-17T11:51:06Z
day: '28'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1093/molbev/msy163
external_id:
  isi:
  - '000452567200006'
  pmid:
  - '30169679'
intvolume: '        35'
isi: 1
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pubmed/30169679
month: '08'
oa: 1
oa_version: Submitted Version
page: 2669 - 2684
pmid: 1
publication: Molecular Biology and Evolution
publication_identifier:
  issn:
  - 0737-4038
publication_status: published
publisher: Oxford University Press
publist_id: '8036'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nonoptimal gene expression creates latent potential for antibiotic resistance
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 35
year: '2018'
...