Evidence map›Paper›PMID 32094499›Full record

ArticleScientific reports2020

Droplet-based digital antibiotic susceptibility screen reveals single-cell clonal heteroresistance in an isogenic bacterial population.

Ott Scheler, Karol Makuch, Pawel R Debski, Michal Horka, Artur Ruszczak, Natalia Pacocha, Krzysztof Sozański, Olli-Pekka Smolander, Witold Postek, Piotr Garstecki

Abstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing 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

43 citing papers in PubMed.

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  12. Habitat fragmentation enhances microbial collective defence.Journal of the Royal Society, Interface · 2025
    Article
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  15. Review
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  19. Time-resolved cell-to-cell heterogeneity ofFrontiers in bioengineering and biotechnology · 2024
    Article
  20. Sensing of Antibiotic-Bacteria Interactions.Antibiotics (Basel, Switzerland) · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Ott SchelerInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland. ott.scheler@taltech.ee.ORCID http://orcid.org/0000-0002-8428-1350
Karol MakuchInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Pawel R DebskiInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Michal HorkaInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Artur RuszczakInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Natalia PacochaInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Krzysztof SozańskiInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Olli-Pekka SmolanderDepartment of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, 12618, Tallinn, Estonia.ORCID http://orcid.org/0000-0002-6795-7734
Witold PostekInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland.
Piotr GarsteckiInstitute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224, Warsaw, Poland. garst@ichf.edu.pl.ORCID http://orcid.org/0000-0001-9101-7163

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Since antibiotic resistance is a major threat to global health, recent observations that the traditional test of minimum inhibitory concentration (MIC) is not informative enough to guide effective antibiotic treatment are alarming. Bacterial heteroresistance, in which seemingly susceptible isogenic bacterial populations contain resistant sub-populations, underlies much of this challenge. To close this gap, here we developed a droplet-based digital MIC screen that constitutes a practical analytical platform for quantifying the single-cell distribution of phenotypic responses to antibiotics, as well as for measuring inoculum effect with high accuracy. We found that antibiotic efficacy is determined by the amount of antibiotic used per bacterial colony forming unit (CFU), not by the absolute antibiotic concentration, as shown by the treatment of beta-lactamase-carrying Escherichia coli with cefotaxime. We also noted that cells exhibited a pronounced clustering phenotype when exposed to near-inhibitory amounts of cefotaxime. Overall, our method facilitates research into the interplay between heteroresistance and antibiotic efficacy, as well as research into the origin and stimulation of heterogeneity by exposure to antibiotics. Due to the absolute bacteria quantification in this digital assay, our method provides a platform for developing reference MIC assays that are robust against inoculum-density variations.

Indexed as

Colony Count, MicrobialDrug Resistance, BacterialAnti-Bacterial Agentsbeta-LactamasesCefotaximeEscherichia coliLab-On-A-Chip DevicesMicrobial Sensitivity TestsMicrofluidicsMicroscopy, ConfocalMutationPhenotypeSingle-Cell AnalysisAnti-Bacterial Agentsbeta-LactamasesCefotaxime

Identifiers

PMID32094499
PMCPMC7039976

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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.