Evidence map›Paper›PMID 37978173›Full record

ArticleNature communications2023

Synthetic genetic oscillators demonstrate the functional importance of phenotypic variation in pneumococcal-host interactions.

Anne-Stéphanie Rueff, Renske van Raaphorst, Surya D Aggarwal, Javier Santos-Moreno, Géraldine Laloux, Yolanda Schaerli, Jeffrey N Weiser, Jan-Willem Veening

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Article
  2. Design of CRISPRi-Based Synthetic Gene Circuits in Bacteria.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Non-invasiveEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024
    Article
  7. Article
  8. Article
  9. An efficientmBio · 2024
    Article
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Anne-Stéphanie RueffDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015, Lausanne, Switzerland.
Renske van RaaphorstDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015, Lausanne, Switzerland.ORCID 0000-0001-7778-5289
Surya D AggarwalDepartment of Microbiology, New York University School of Medicine, New York, NY, USA.ORCID 0000-0001-8900-6684
Javier Santos-MorenoDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015, Lausanne, Switzerland.ORCID 0000-0001-6268-2623
Géraldine Lalouxde Duve Institute, UCLouvain, 75 Avenue Hippocrate, 1200, Brussels, Belgium.ORCID 0000-0003-3230-1679
Yolanda SchaerliDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015, Lausanne, Switzerland.ORCID 0000-0002-9083-7343
Jeffrey N WeiserDepartment of Microbiology, New York University School of Medicine, New York, NY, USA.
Jan-Willem VeeningDepartment of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, CH-1015, Lausanne, Switzerland. Jan-Willem.Veening@unil.ch.ORCID 0000-0002-3162-6634

Funding

ROLE OF OPACITY VARIATION IN PNEUMOCOCCAL PATHOGENESISR01AI038446 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WEISER, JEFFREY NEAL · 1996 to 2019
$7.4M
Mechanisms of Pneumococcal Persistence During CarriageR37AI038446 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jeffrey Neal Weiser · 2020 to 2026
$3.8M
Targeting Pneumococcal TransmissionR01AI150893 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI WEISER, JEFFREY NEAL · 2020 to 2024
$3.3M
NIAID NIH HHS R01 AI150893NIAID NIH HHS R37 AI038446
6 · The paper itself

Abstract

Phenotypic variation is the phenomenon in which clonal cells display different traits even under identical environmental conditions. This plasticity is thought to be important for processes including bacterial virulence, but direct evidence for its relevance is often lacking. For instance, variation in capsule production in the human pathogen Streptococcus pneumoniae has been linked to different clinical outcomes, but the exact relationship between variation and pathogenesis is not well understood due to complex natural regulation. In this study, we use synthetic oscillatory gene regulatory networks (GRNs) based on CRISPR interference (CRISPRi) together with live cell imaging and cell tracking within microfluidics devices to mimic and test the biological function of bacterial phenotypic variation. We provide a universally applicable approach for engineering intricate GRNs using only two components: dCas9 and extended sgRNAs (ext-sgRNAs). Our findings demonstrate that variation in capsule production is beneficial for pneumococcal fitness in traits associated with pathogenesis providing conclusive evidence for this longstanding question.

Indexed as

RNA, Guide, CRISPR-Cas SystemsStreptococcus pneumoniaeBiological Variation, PopulationHumansPhenotypeRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID37978173
PMCPMC10656556

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.