Evidence map›Paper›PMID 37770760›Full record

ArticleNature microbiology2023

Systematic analysis of drug combinations against Gram-positive bacteria.

Elisabetta Cacace, Vladislav Kim, Vallo Varik, Michael Knopp, Manuela Tietgen, Amber Brauer-Nikonow, Kemal Inecik, André Mateus, Alessio Milanese, Marita Torrissen Mårli and 10 more

Abstract read
In one paragraph

Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 2 pooled it
–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

42 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Article
  4. The phenotypic landscape of the model firmicuteProceedings of the National Academy of Sciences of the United States of America · 2026
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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

20 authors.

Elisabetta CacaceEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0001-8239-0353
Vladislav KimEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0001-5061-7285
Vallo VarikEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0001-6900-6986
Michael KnoppEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0002-8218-3263
Manuela TietgenGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt am Main, Germany.ORCID 0000-0001-5117-4340
Amber Brauer-NikonowEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0003-4146-2458
Kemal InecikEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0001-7379-9093
André MateusEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Alessio MilaneseEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.ORCID 0000-0002-7050-2239
Marita Torrissen MårliFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.ORCID 0009-0001-1535-7032
Karin MitoschEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Joel SelkrigEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Ana Rita BrochadoEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0003-1703-383X
Oscar P KuipersDepartment of Molecular Genetics, Groningen Molecular Biology and Biotechnology Institute, University of Groningen, Groningen, the Netherlands.ORCID 0000-0001-5596-7735
Morten KjosFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.ORCID 0000-0003-4448-9082
Georg ZellerEuropean Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany.
Mikhail M SavitskiEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.ORCID 0000-0003-2011-9247
Stephan GöttigGoethe University Frankfurt, University Hospital, Institute for Medical Microbiology and Infection Control, Frankfurt am Main, Germany.ORCID 0000-0001-6896-5309
Wolfgang HuberEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany.
Athanasios TypasEuropean Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany. typas@embl.de.ORCID 0000-0002-0797-9018

Funding

European Molecular Biology Laboratory (EMBL Heidelberg) Internal budgetJoint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance) CombinatorialsJoint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance) Disrupt
6 · The paper itself

Abstract

Drug combinations can expand options for antibacterial therapies but have not been systematically tested in Gram-positive species. We profiled ~8,000 combinations of 65 antibacterial drugs against the model species Bacillus subtilis and two prominent pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Thereby, we recapitulated previously known drug interactions, but also identified ten times more novel interactions in the pathogen S. aureus, including 150 synergies. We showed that two synergies were equally effective against multidrug-resistant S. aureus clinical isolates in vitro and in vivo. Interactions were largely species-specific and synergies were distinct from those of Gram-negative species, owing to cell surface and drug uptake differences. We also tested 2,728 combinations of 44 commonly prescribed non-antibiotic drugs with 62 drugs with antibacterial activity against S. aureus and identified numerous antagonisms that might compromise the efficacy of antimicrobial therapies. We identified even more synergies and showed that the anti-aggregant ticagrelor synergized with cationic antibiotics by modifying the surface charge of S. aureus. All data can be browsed in an interactive interface ( https://apps.embl.de/combact/ ).

Indexed as

Methicillin-Resistant Staphylococcus aureusStaphylococcus aureusAnti-Bacterial AgentsDrug CombinationsGram-Positive BacteriaAnti-Bacterial AgentsDrug Combinations

Identifiers

PMID37770760
PMCPMC10627819

What OpenQuestion holds

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Registered trials

None linked

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.