---
_id: '822'
abstract:
- lang: eng
  text: 'Polymicrobial infections constitute small ecosystems that accommodate several
    bacterial species. Commonly, these bacteria are investigated in isolation. However,
    it is unknown to what extent the isolates interact and whether their interactions
    alter bacterial growth and ecosystem resilience in the presence and absence of
    antibiotics. We quantified the complete ecological interaction network for 72
    bacterial isolates collected from 23 individuals diagnosed with polymicrobial
    urinary tract infections and found that most interactions cluster based on evolutionary
    relatedness. Statistical network analysis revealed that competitive and cooperative
    reciprocal interactions are enriched in the global network, while cooperative
    interactions are depleted in the individual host community networks. A population
    dynamics model parameterized by our measurements suggests that interactions restrict
    community stability, explaining the observed species diversity of these communities.
    We further show that the clinical isolates frequently protect each other from
    clinically relevant antibiotics. Together, these results highlight that ecological
    interactions are crucial for the growth and survival of bacteria in polymicrobial
    infection communities and affect their assembly and resilience. '
article_processing_charge: No
author:
- first_name: Marjon
  full_name: De Vos, Marjon
  id: 3111FFAC-F248-11E8-B48F-1D18A9856A87
  last_name: De Vos
- first_name: Marcin P
  full_name: Zagórski, Marcin P
  id: 343DA0DC-F248-11E8-B48F-1D18A9856A87
  last_name: Zagórski
  orcid: 0000-0001-7896-7762
- first_name: Alan
  full_name: Mcnally, Alan
  last_name: Mcnally
- 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: de Vos M, Zagórski MP, Mcnally A, Bollenbach MT. Interaction networks, ecological
    stability, and collective antibiotic tolerance in polymicrobial infections. <i>PNAS</i>.
    2017;114(40):10666-10671. doi:<a href="https://doi.org/10.1073/pnas.1713372114">10.1073/pnas.1713372114</a>
  apa: de Vos, M., Zagórski, M. P., Mcnally, A., &#38; Bollenbach, M. T. (2017). Interaction
    networks, ecological stability, and collective antibiotic tolerance in polymicrobial
    infections. <i>PNAS</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1713372114">https://doi.org/10.1073/pnas.1713372114</a>
  chicago: Vos, Marjon de, Marcin P Zagórski, Alan Mcnally, and Mark Tobias Bollenbach.
    “Interaction Networks, Ecological Stability, and Collective Antibiotic Tolerance
    in Polymicrobial Infections.” <i>PNAS</i>. National Academy of Sciences, 2017.
    <a href="https://doi.org/10.1073/pnas.1713372114">https://doi.org/10.1073/pnas.1713372114</a>.
  ieee: M. de Vos, M. P. Zagórski, A. Mcnally, and M. T. Bollenbach, “Interaction
    networks, ecological stability, and collective antibiotic tolerance in polymicrobial
    infections,” <i>PNAS</i>, vol. 114, no. 40. National Academy of Sciences, pp.
    10666–10671, 2017.
  ista: de Vos M, Zagórski MP, Mcnally A, Bollenbach MT. 2017. Interaction networks,
    ecological stability, and collective antibiotic tolerance in polymicrobial infections.
    PNAS. 114(40), 10666–10671.
  mla: de Vos, Marjon, et al. “Interaction Networks, Ecological Stability, and Collective
    Antibiotic Tolerance in Polymicrobial Infections.” <i>PNAS</i>, vol. 114, no.
    40, National Academy of Sciences, 2017, pp. 10666–71, doi:<a href="https://doi.org/10.1073/pnas.1713372114">10.1073/pnas.1713372114</a>.
  short: M. de Vos, M.P. Zagórski, A. Mcnally, M.T. Bollenbach, PNAS 114 (2017) 10666–10671.
corr_author: '1'
date_created: 2018-12-11T11:48:41Z
date_published: 2017-10-03T00:00:00Z
date_updated: 2025-07-10T11:55:08Z
day: '03'
department:
- _id: ToBo
doi: 10.1073/pnas.1713372114
ec_funded: 1
external_id:
  isi:
  - '000412130500061'
  pmid:
  - '28923953'
intvolume: '       114'
isi: 1
issue: '40'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635929/
month: '10'
oa: 1
oa_version: Submitted Version
page: 10666 - 10671
pmid: 1
project:
- _id: 25E83C2C-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '303507'
  name: Optimality principles in responses to antibiotics
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P27201-B22
  name: Revealing the mechanisms underlying drug interactions
publication: PNAS
publication_identifier:
  issn:
  - 0027-8424
publication_status: published
publisher: National Academy of Sciences
publist_id: '6827'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Interaction networks, ecological stability, and collective antibiotic tolerance
  in polymicrobial infections
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 114
year: '2017'
...
---
OA_place: repository
OA_type: green
_id: '1571'
abstract:
- lang: eng
  text: Epistatic interactions can frustrate and shape evolutionary change. Indeed,
    phenotypes may fail to evolve when essential mutations are only accessible through
    positive selection if they are fixed simultaneously. How environmental variability
    affects such constraints is poorly understood. Here, we studied genetic constraints
    in fixed and fluctuating environments using the Escherichia coli lac operon as
    a model system for genotype-environment interactions. We found that, in different
    fixed environments, all trajectories that were reconstructed by applying point
    mutations within the transcription factor-operator interface became trapped at
    suboptima, where no additional improvements were possible. Paradoxically, repeated
    switching between these same environments allows unconstrained adaptation by continuous
    improvements. This evolutionary mode is explained by pervasive cross-environmental
    tradeoffs that reposition the peaks in such a way that trapped genotypes can repeatedly
    climb ascending slopes and hence, escape adaptive stasis. Using a Markov approach,
    we developed a mathematical framework to quantify the landscape-crossing rates
    and show that this ratchet-like adaptive mechanism is robust in a wide spectrum
    of fluctuating environments. Overall, this study shows that genetic constraints
    can be overcome by environmental change and that crossenvironmental tradeoffs
    do not necessarily impede but also, can facilitate adaptive evolution. Because
    tradeoffs and environmental variability are ubiquitous in nature, we speculate
    this evolutionary mode to be of general relevance.
acknowledgement: This work is part of the research program of the Foundation for Fundamental
  Research on Matter, which is part of the Netherlands Organization for Scientific
  Research (NWO). M.G.J.d.V. was (partially) funded by NWO Earth and Life Sciences
  (ALW), project 863.14.015. We thank D. M. Weinreich, J. A. G. M. de Visser, T. Paixão,
  J. Polechová, T. Friedlander, and A. E. Mayo for reading and commenting on earlier
  versions of the manuscript and B. Houchmandzadeh, O. Rivoire, and M. Hemery for
  discussions and suggestions on the Markov computation. Furthermore, we thank F.
  J. Poelwijk for sharing plasmid pCascade5 and pRD007 and Y. Yokobayashi for sharing
  plasmid pINV-110. We also thank the anonymous reviewers for remarks on the initial
  version of the manuscript.
article_processing_charge: No
article_type: original
author:
- first_name: Marjon
  full_name: De Vos, Marjon
  id: 3111FFAC-F248-11E8-B48F-1D18A9856A87
  last_name: De Vos
- first_name: Alexandre
  full_name: Dawid, Alexandre
  last_name: Dawid
- first_name: Vanda
  full_name: Šunderlíková, Vanda
  last_name: Šunderlíková
- first_name: Sander
  full_name: Tans, Sander
  last_name: Tans
citation:
  ama: de Vos M, Dawid A, Šunderlíková V, Tans S. Breaking evolutionary constraint
    with a tradeoff ratchet. <i>Proceedings of the National Academy of Sciences</i>.
    2015;112(48):14906-14911. doi:<a href="https://doi.org/10.1073/pnas.1510282112">10.1073/pnas.1510282112</a>
  apa: de Vos, M., Dawid, A., Šunderlíková, V., &#38; Tans, S. (2015). Breaking evolutionary
    constraint with a tradeoff ratchet. <i>Proceedings of the National Academy of
    Sciences</i>. National Academy of Sciences. <a href="https://doi.org/10.1073/pnas.1510282112">https://doi.org/10.1073/pnas.1510282112</a>
  chicago: Vos, Marjon de, Alexandre Dawid, Vanda Šunderlíková, and Sander Tans. “Breaking
    Evolutionary Constraint with a Tradeoff Ratchet.” <i>Proceedings of the National
    Academy of Sciences</i>. National Academy of Sciences, 2015. <a href="https://doi.org/10.1073/pnas.1510282112">https://doi.org/10.1073/pnas.1510282112</a>.
  ieee: M. de Vos, A. Dawid, V. Šunderlíková, and S. Tans, “Breaking evolutionary
    constraint with a tradeoff ratchet,” <i>Proceedings of the National Academy of
    Sciences</i>, vol. 112, no. 48. National Academy of Sciences, pp. 14906–14911,
    2015.
  ista: de Vos M, Dawid A, Šunderlíková V, Tans S. 2015. Breaking evolutionary constraint
    with a tradeoff ratchet. Proceedings of the National Academy of Sciences. 112(48),
    14906–14911.
  mla: de Vos, Marjon, et al. “Breaking Evolutionary Constraint with a Tradeoff Ratchet.”
    <i>Proceedings of the National Academy of Sciences</i>, vol. 112, no. 48, National
    Academy of Sciences, 2015, pp. 14906–11, doi:<a href="https://doi.org/10.1073/pnas.1510282112">10.1073/pnas.1510282112</a>.
  short: M. de Vos, A. Dawid, V. Šunderlíková, S. Tans, Proceedings of the National
    Academy of Sciences 112 (2015) 14906–14911.
date_created: 2018-12-11T11:52:47Z
date_published: 2015-12-01T00:00:00Z
date_updated: 2025-09-23T08:03:27Z
day: '01'
department:
- _id: ToBo
doi: 10.1073/pnas.1510282112
external_id:
  isi:
  - '000365988900054'
  pmid:
  - '26567153'
intvolume: '       112'
isi: 1
issue: '48'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://pmc.ncbi.nlm.nih.gov/articles/PMC4672788/
month: '12'
oa: 1
oa_version: Submitted Version
page: 14906 - 14911
pmid: 1
publication: Proceedings of the National Academy of Sciences
publication_status: published
publisher: National Academy of Sciences
publist_id: '5600'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Breaking evolutionary constraint with a tradeoff ratchet
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 112
year: '2015'
...
---
_id: '2220'
abstract:
- lang: eng
  text: In this issue of Chemistry & Biology, Cokol and colleagues report a systematic
    study of drug interactions between antifungal compounds. Suppressive drug interactions
    occur more frequently than previously realized and come in different flavors with
    interesting implications.
article_processing_charge: No
author:
- first_name: Marjon
  full_name: De Vos, Marjon
  id: 3111FFAC-F248-11E8-B48F-1D18A9856A87
  last_name: De Vos
- 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: de Vos M, Bollenbach MT. Suppressive drug interactions between antifungals.
    <i>Chemistry and Biology</i>. 2014;21(4):439-440. doi:<a href="https://doi.org/10.1016/j.chembiol.2014.04.004">10.1016/j.chembiol.2014.04.004</a>
  apa: de Vos, M., &#38; Bollenbach, M. T. (2014). Suppressive drug interactions between
    antifungals. <i>Chemistry and Biology</i>. Cell Press. <a href="https://doi.org/10.1016/j.chembiol.2014.04.004">https://doi.org/10.1016/j.chembiol.2014.04.004</a>
  chicago: Vos, Marjon de, and Mark Tobias Bollenbach. “Suppressive Drug Interactions
    between Antifungals.” <i>Chemistry and Biology</i>. Cell Press, 2014. <a href="https://doi.org/10.1016/j.chembiol.2014.04.004">https://doi.org/10.1016/j.chembiol.2014.04.004</a>.
  ieee: M. de Vos and M. T. Bollenbach, “Suppressive drug interactions between antifungals,”
    <i>Chemistry and Biology</i>, vol. 21, no. 4. Cell Press, pp. 439–440, 2014.
  ista: de Vos M, Bollenbach MT. 2014. Suppressive drug interactions between antifungals.
    Chemistry and Biology. 21(4), 439–440.
  mla: de Vos, Marjon, and Mark Tobias Bollenbach. “Suppressive Drug Interactions
    between Antifungals.” <i>Chemistry and Biology</i>, vol. 21, no. 4, Cell Press,
    2014, pp. 439–40, doi:<a href="https://doi.org/10.1016/j.chembiol.2014.04.004">10.1016/j.chembiol.2014.04.004</a>.
  short: M. de Vos, M.T. Bollenbach, Chemistry and Biology 21 (2014) 439–440.
corr_author: '1'
date_created: 2018-12-11T11:56:24Z
date_published: 2014-04-24T00:00:00Z
date_updated: 2025-09-29T11:28:57Z
day: '24'
department:
- _id: ToBo
doi: 10.1016/j.chembiol.2014.04.004
external_id:
  isi:
  - '000335431300005'
  pmid:
  - '24766845'
intvolume: '        21'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pubmed/24766845
month: '04'
oa: 1
oa_version: Published Version
page: 439 - 440
pmid: 1
publication: Chemistry and Biology
publication_identifier:
  issn:
  - 1074-5521
publication_status: published
publisher: Cell Press
publist_id: '4747'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Suppressive drug interactions between antifungals
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 21
year: '2014'
...
---
_id: '2810'
abstract:
- lang: eng
  text: The epistatic interactions that underlie evolutionary constraint have mainly
    been studied for constant external conditions. However, environmental changes
    may modulate epistasis and hence affect genetic constraints. Here we investigate
    genetic constraints in the adaptive evolution of a novel regulatory function in
    variable environments, using the lac repressor, LacI, as a model system. We have
    systematically reconstructed mutational trajectories from wild type LacI to three
    different variants that each exhibit an inverse response to the inducing ligand
    IPTG, and analyzed the higher-order interactions between genetic and environmental
    changes. We find epistasis to depend strongly on the environment. As a result,
    mutational steps essential to inversion but inaccessible by positive selection
    in one environment, become accessible in another. We present a graphical method
    to analyze the observed complex higher-order interactions between multiple mutations
    and environmental change, and show how the interactions can be explained by a
    combination of mutational effects on allostery and thermodynamic stability. This
    dependency of genetic constraint on the environment should fundamentally affect
    evolutionary dynamics and affects the interpretation of phylogenetic data.
article_number: e1003580
article_processing_charge: No
author:
- first_name: Marjon
  full_name: De Vos, Marjon
  id: 3111FFAC-F248-11E8-B48F-1D18A9856A87
  last_name: De Vos
- first_name: Frank
  full_name: Poelwijk, Frank
  last_name: Poelwijk
- first_name: Nico
  full_name: Battich, Nico
  last_name: Battich
- first_name: Joseph
  full_name: Ndika, Joseph
  last_name: Ndika
- first_name: Sander
  full_name: Tans, Sander
  last_name: Tans
citation:
  ama: de Vos M, Poelwijk F, Battich N, Ndika J, Tans S. Environmental dependence
    of genetic constraint. <i>PLoS Genetics</i>. 2013;9(6). doi:<a href="https://doi.org/10.1371/journal.pgen.1003580">10.1371/journal.pgen.1003580</a>
  apa: de Vos, M., Poelwijk, F., Battich, N., Ndika, J., &#38; Tans, S. (2013). Environmental
    dependence of genetic constraint. <i>PLoS Genetics</i>. Public Library of Science.
    <a href="https://doi.org/10.1371/journal.pgen.1003580">https://doi.org/10.1371/journal.pgen.1003580</a>
  chicago: Vos, Marjon de, Frank Poelwijk, Nico Battich, Joseph Ndika, and Sander
    Tans. “Environmental Dependence of Genetic Constraint.” <i>PLoS Genetics</i>.
    Public Library of Science, 2013. <a href="https://doi.org/10.1371/journal.pgen.1003580">https://doi.org/10.1371/journal.pgen.1003580</a>.
  ieee: M. de Vos, F. Poelwijk, N. Battich, J. Ndika, and S. Tans, “Environmental
    dependence of genetic constraint,” <i>PLoS Genetics</i>, vol. 9, no. 6. Public
    Library of Science, 2013.
  ista: de Vos M, Poelwijk F, Battich N, Ndika J, Tans S. 2013. Environmental dependence
    of genetic constraint. PLoS Genetics. 9(6), e1003580.
  mla: de Vos, Marjon, et al. “Environmental Dependence of Genetic Constraint.” <i>PLoS
    Genetics</i>, vol. 9, no. 6, e1003580, Public Library of Science, 2013, doi:<a
    href="https://doi.org/10.1371/journal.pgen.1003580">10.1371/journal.pgen.1003580</a>.
  short: M. de Vos, F. Poelwijk, N. Battich, J. Ndika, S. Tans, PLoS Genetics 9 (2013).
date_created: 2018-12-11T11:59:43Z
date_published: 2013-06-27T00:00:00Z
date_updated: 2025-09-29T14:05:09Z
day: '27'
ddc:
- '570'
department:
- _id: ToBo
doi: 10.1371/journal.pgen.1003580
external_id:
  isi:
  - '000321222600053'
file:
- access_level: open_access
  checksum: 7a4736dd80496d29ff6908b6f2329b4e
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  creator: system
  date_created: 2018-12-12T10:08:51Z
  date_updated: 2020-07-14T12:45:48Z
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  file_name: IST-2016-412-v1+1_journal.pgen.1003580.pdf
  file_size: 474655
  relation: main_file
file_date_updated: 2020-07-14T12:45:48Z
has_accepted_license: '1'
intvolume: '         9'
isi: 1
issue: '6'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
publication: PLoS Genetics
publication_status: published
publisher: Public Library of Science
publist_id: '4075'
pubrep_id: '412'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Environmental dependence of genetic constraint
tmp:
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  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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 9
year: '2013'
...