---
_id: '8997'
abstract:
- lang: eng
  text: Phenomenological relations such as Ohm’s or Fourier’s law have a venerable
    history in physics but are still scarce in biology. This situation restrains predictive
    theory. Here, we build on bacterial “growth laws,” which capture physiological
    feedback between translation and cell growth, to construct a minimal biophysical
    model for the combined action of ribosome-targeting antibiotics. Our model predicts
    drug interactions like antagonism or synergy solely from responses to individual
    drugs. We provide analytical results for limiting cases, which agree well with
    numerical results. We systematically refine the model by including direct physical
    interactions of different antibiotics on the ribosome. In a limiting case, our
    model provides a mechanistic underpinning for recent predictions of higher-order
    interactions that were derived using entropy maximization. We further refine the
    model to include the effects of antibiotics that mimic starvation and the presence
    of resistance genes. We describe the impact of a starvation-mimicking antibiotic
    on drug interactions analytically and verify it experimentally. Our extended model
    suggests a change in the type of drug interaction that depends on the strength
    of resistance, which challenges established rescaling paradigms. We experimentally
    show that the presence of unregulated resistance genes can lead to altered drug
    interaction, which agrees with the prediction of the model. While minimal, the
    model is readily adaptable and opens the door to predicting interactions of second
    and higher-order in a broad range of biological systems.
acknowledgement: 'This work was supported in part by Tum stipend of Knafelj foundation
  (to B.K.), Austrian Science Fund (FWF) standalone grants P 27201-B22 (to T.B.) and
  P 28844(to G.T.), HFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation
  (DFG) individual grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)
  Collaborative Research Centre (SFB) 1310 (to T.B.). '
article_number: e1008529
article_processing_charge: Yes
article_type: original
author:
- first_name: Bor
  full_name: Kavcic, Bor
  id: 350F91D2-F248-11E8-B48F-1D18A9856A87
  last_name: Kavcic
  orcid: 0000-0001-6041-254X
- first_name: Gašper
  full_name: Tkačik, Gašper
  id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
  last_name: Tkačik
  orcid: 0000-0002-6699-1455
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
citation:
  ama: Kavcic B, Tkačik G, Bollenbach MT. Minimal biophysical model of combined antibiotic
    action. <i>PLOS Computational Biology</i>. 2021;17. doi:<a href="https://doi.org/10.1371/journal.pcbi.1008529">10.1371/journal.pcbi.1008529</a>
  apa: Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2021). Minimal biophysical
    model of combined antibiotic action. <i>PLOS Computational Biology</i>. Public
    Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1008529">https://doi.org/10.1371/journal.pcbi.1008529</a>
  chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Minimal Biophysical
    Model of Combined Antibiotic Action.” <i>PLOS Computational Biology</i>. Public
    Library of Science, 2021. <a href="https://doi.org/10.1371/journal.pcbi.1008529">https://doi.org/10.1371/journal.pcbi.1008529</a>.
  ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Minimal biophysical model of
    combined antibiotic action,” <i>PLOS Computational Biology</i>, vol. 17. Public
    Library of Science, 2021.
  ista: Kavcic B, Tkačik G, Bollenbach MT. 2021. Minimal biophysical model of combined
    antibiotic action. PLOS Computational Biology. 17, e1008529.
  mla: Kavcic, Bor, et al. “Minimal Biophysical Model of Combined Antibiotic Action.”
    <i>PLOS Computational Biology</i>, vol. 17, e1008529, Public Library of Science,
    2021, doi:<a href="https://doi.org/10.1371/journal.pcbi.1008529">10.1371/journal.pcbi.1008529</a>.
  short: B. Kavcic, G. Tkačik, M.T. Bollenbach, PLOS Computational Biology 17 (2021).
date_created: 2021-01-08T07:16:18Z
date_published: 2021-01-07T00:00:00Z
date_updated: 2024-02-21T12:41:41Z
day: '07'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1008529
external_id:
  isi:
  - '000608045000010'
file:
- access_level: open_access
  checksum: e29f2b42651bef8e034781de8781ffac
  content_type: application/pdf
  creator: dernst
  date_created: 2021-02-04T12:30:48Z
  date_updated: 2021-02-04T12:30:48Z
  file_id: '9092'
  file_name: 2021_PlosComBio_Kavcic.pdf
  file_size: 3690053
  relation: main_file
  success: 1
file_date_updated: 2021-02-04T12:30:48Z
has_accepted_license: '1'
intvolume: '        17'
isi: 1
keyword:
- Modelling and Simulation
- Genetics
- Molecular Biology
- Antibiotics
- Drug interactions
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P28844-B27
  name: Biophysics of information processing in gene regulation
publication: PLOS Computational Biology
publication_identifier:
  issn:
  - 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
  record:
  - id: '7673'
    relation: earlier_version
    status: public
  - id: '8930'
    relation: research_data
    status: public
status: public
title: Minimal biophysical model of combined antibiotic action
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: 17
year: '2021'
...
---
_id: '9387'
abstract:
- lang: eng
  text: We report the complete analysis of a deterministic model of deleterious mutations
    and negative selection against them at two haploid loci without recombination.
    As long as mutation is a weaker force than selection, mutant alleles remain rare
    at the only stable equilibrium, and otherwise, a variety of dynamics are possible.
    If the mutation-free genotype is absent, generally the only stable equilibrium
    is the one that corresponds to fixation of the mutant allele at the locus where
    it is less deleterious. This result suggests that fixation of a deleterious allele
    that follows a click of the Muller’s ratchet is governed by natural selection,
    instead of random drift.
acknowledgement: This work was supported by the Russian Science Foundation grant N
  16-14-10173.
article_number: '110729'
article_processing_charge: No
article_type: original
author:
- first_name: Kseniia
  full_name: Khudiakova, Kseniia
  id: 4E6DC800-AE37-11E9-AC72-31CAE5697425
  last_name: Khudiakova
  orcid: 0000-0002-6246-1465
- first_name: Tatiana Yu.
  full_name: Neretina, Tatiana Yu.
  last_name: Neretina
- first_name: Alexey S.
  full_name: Kondrashov, Alexey S.
  last_name: Kondrashov
citation:
  ama: Khudiakova K, Neretina TY, Kondrashov AS. Two linked loci under mutation-selection
    balance and Muller’s ratchet. <i>Journal of Theoretical Biology</i>. 2021;524.
    doi:<a href="https://doi.org/10.1016/j.jtbi.2021.110729">10.1016/j.jtbi.2021.110729</a>
  apa: Khudiakova, K., Neretina, T. Y., &#38; Kondrashov, A. S. (2021). Two linked
    loci under mutation-selection balance and Muller’s ratchet. <i>Journal of Theoretical
    Biology</i>. Elsevier . <a href="https://doi.org/10.1016/j.jtbi.2021.110729">https://doi.org/10.1016/j.jtbi.2021.110729</a>
  chicago: Khudiakova, Kseniia, Tatiana Yu. Neretina, and Alexey S. Kondrashov. “Two
    Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” <i>Journal
    of Theoretical Biology</i>. Elsevier , 2021. <a href="https://doi.org/10.1016/j.jtbi.2021.110729">https://doi.org/10.1016/j.jtbi.2021.110729</a>.
  ieee: K. Khudiakova, T. Y. Neretina, and A. S. Kondrashov, “Two linked loci under
    mutation-selection balance and Muller’s ratchet,” <i>Journal of Theoretical Biology</i>,
    vol. 524. Elsevier , 2021.
  ista: Khudiakova K, Neretina TY, Kondrashov AS. 2021. Two linked loci under mutation-selection
    balance and Muller’s ratchet. Journal of Theoretical Biology. 524, 110729.
  mla: Khudiakova, Kseniia, et al. “Two Linked Loci under Mutation-Selection Balance
    and Muller’s Ratchet.” <i>Journal of Theoretical Biology</i>, vol. 524, 110729,
    Elsevier , 2021, doi:<a href="https://doi.org/10.1016/j.jtbi.2021.110729">10.1016/j.jtbi.2021.110729</a>.
  short: K. Khudiakova, T.Y. Neretina, A.S. Kondrashov, Journal of Theoretical Biology
    524 (2021).
date_created: 2021-05-12T05:58:42Z
date_published: 2021-04-24T00:00:00Z
date_updated: 2023-08-08T13:32:40Z
day: '24'
department:
- _id: GradSch
doi: 10.1016/j.jtbi.2021.110729
external_id:
  isi:
  - '000659161500002'
intvolume: '       524'
isi: 1
keyword:
- General Biochemistry
- Genetics and Molecular Biology
- Modelling and Simulation
- Statistics and Probability
- General Immunology and Microbiology
- Applied Mathematics
- General Agricultural and Biological Sciences
- General Medicine
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.biorxiv.org/content/10.1101/477489v1
month: '04'
oa: 1
oa_version: Preprint
publication: Journal of Theoretical Biology
publication_identifier:
  issn:
  - 0022-5193
publication_status: published
publisher: 'Elsevier '
quality_controlled: '1'
status: public
title: Two linked loci under mutation-selection balance and Muller’s ratchet
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 524
year: '2021'
...
---
_id: '8767'
abstract:
- lang: eng
  text: Resources are rarely distributed uniformly within a population. Heterogeneity
    in the concentration of a drug, the quality of breeding sites, or wealth can all
    affect evolutionary dynamics. In this study, we represent a collection of properties
    affecting the fitness at a given location using a color. A green node is rich
    in resources while a red node is poorer. More colors can represent a broader spectrum
    of resource qualities. For a population evolving according to the birth-death
    Moran model, the first question we address is which structures, identified by
    graph connectivity and graph coloring, are evolutionarily equivalent. We prove
    that all properly two-colored, undirected, regular graphs are evolutionarily equivalent
    (where “properly colored” means that no two neighbors have the same color). We
    then compare the effects of background heterogeneity on properly two-colored graphs
    to those with alternative schemes in which the colors are permuted. Finally, we
    discuss dynamic coloring as a model for spatiotemporal resource fluctuations,
    and we illustrate that random dynamic colorings often diminish the effects of
    background heterogeneity relative to a proper two-coloring.
acknowledgement: 'We thank Igor Erovenko for many helpful comments on an earlier version
  of this paper. : Army Research Laboratory (grant W911NF-18-2-0265) (M.A.N.); the
  Bill & Melinda Gates Foundation (grant OPP1148627) (M.A.N.); the NVIDIA Corporation
  (A.M.). The funders had no role in study design, data collection and analysis, decision
  to publish, or preparation of the manuscript.'
article_number: e1008402
article_processing_charge: No
article_type: original
author:
- first_name: Kamran
  full_name: Kaveh, Kamran
  last_name: Kaveh
- first_name: Alex
  full_name: McAvoy, Alex
  last_name: McAvoy
- first_name: Krishnendu
  full_name: Chatterjee, Krishnendu
  id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
  last_name: Chatterjee
  orcid: 0000-0002-4561-241X
- first_name: Martin A.
  full_name: Nowak, Martin A.
  last_name: Nowak
citation:
  ama: Kaveh K, McAvoy A, Chatterjee K, Nowak MA. The Moran process on 2-chromatic
    graphs. <i>PLOS Computational Biology</i>. 2020;16(11). doi:<a href="https://doi.org/10.1371/journal.pcbi.1008402">10.1371/journal.pcbi.1008402</a>
  apa: Kaveh, K., McAvoy, A., Chatterjee, K., &#38; Nowak, M. A. (2020). The Moran
    process on 2-chromatic graphs. <i>PLOS Computational Biology</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.pcbi.1008402">https://doi.org/10.1371/journal.pcbi.1008402</a>
  chicago: Kaveh, Kamran, Alex McAvoy, Krishnendu Chatterjee, and Martin A. Nowak.
    “The Moran Process on 2-Chromatic Graphs.” <i>PLOS Computational Biology</i>.
    Public Library of Science, 2020. <a href="https://doi.org/10.1371/journal.pcbi.1008402">https://doi.org/10.1371/journal.pcbi.1008402</a>.
  ieee: K. Kaveh, A. McAvoy, K. Chatterjee, and M. A. Nowak, “The Moran process on
    2-chromatic graphs,” <i>PLOS Computational Biology</i>, vol. 16, no. 11. Public
    Library of Science, 2020.
  ista: Kaveh K, McAvoy A, Chatterjee K, Nowak MA. 2020. The Moran process on 2-chromatic
    graphs. PLOS Computational Biology. 16(11), e1008402.
  mla: Kaveh, Kamran, et al. “The Moran Process on 2-Chromatic Graphs.” <i>PLOS Computational
    Biology</i>, vol. 16, no. 11, e1008402, Public Library of Science, 2020, doi:<a
    href="https://doi.org/10.1371/journal.pcbi.1008402">10.1371/journal.pcbi.1008402</a>.
  short: K. Kaveh, A. McAvoy, K. Chatterjee, M.A. Nowak, PLOS Computational Biology
    16 (2020).
date_created: 2020-11-18T07:20:23Z
date_published: 2020-11-05T00:00:00Z
date_updated: 2023-08-22T12:49:18Z
day: '05'
ddc:
- '000'
department:
- _id: KrCh
doi: 10.1371/journal.pcbi.1008402
external_id:
  isi:
  - '000591317200004'
file:
- access_level: open_access
  checksum: 555456dd0e47bcf9e0994bcb95577e88
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-18T07:26:10Z
  date_updated: 2020-11-18T07:26:10Z
  file_id: '8768'
  file_name: 2020_PlosCompBio_Kaveh.pdf
  file_size: 2498594
  relation: main_file
  success: 1
file_date_updated: 2020-11-18T07:26:10Z
has_accepted_license: '1'
intvolume: '        16'
isi: 1
issue: '11'
keyword:
- Ecology
- Modelling and Simulation
- Computational Theory and Mathematics
- Genetics
- Ecology
- Evolution
- Behavior and Systematics
- Molecular Biology
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: PLOS Computational Biology
publication_identifier:
  eissn:
  - 1553-7358
  issn:
  - 1553-734X
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: The Moran process on 2-chromatic graphs
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: 16
year: '2020'
...