Evidence map›Paper›PMID 38585790›Full record

ArticlebioRxiv : the preprint server for biology2024

Massively parallel combination screen reveals small molecule sensitization of antibiotic-resistant Gram-negative ESKAPE pathogens.

Megan W Tse, Meilin Zhu, Benjamin Peters, Efrat Hamami, Julie Chen, Kathleen P Davis, Samuel Nitz, Juliane Weller, Thulasi Warrier, Diana K Hunt and 13 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 3 institutions in 3 countries.

Megan W TseDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-4968-7072
Meilin ZhuDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0003-1302-4020
Benjamin PetersBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Efrat HamamiDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.
Julie ChenDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0003-4648-7478
Kathleen P DavisDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.
Samuel NitzDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0003-3050-8000
Juliane WellerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-1310-6168
Thulasi WarrierBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0000-0002-4384-0873
Diana K HuntBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Yoelkys MoralesDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.
Tomohiko KawateBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Jeffrey L GaulinBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Jon H ComeBroad Institute of MIT and Harvard, Cambridge, MA 02142.ORCID 0009-0006-8463-4247
Juan Hernandez-BirdDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0000-0002-6106-2438
Wenwen HuoDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0000-0001-5112-1951
Isabelle NeisewanderDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0009-0004-6328-7050
Laura L KiesslingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0001-6829-1500
Deborah T HungBroad Institute of MIT and Harvard, Cambridge, MA 02142.
Joan MecsasDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0000-0001-6829-1500
Bree B AldridgeDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0000-0003-2236-1424
Ralph R IsbergDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, & Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Boston, Massachusetts, 02111.ORCID 0000-0002-8330-3554
Paul C BlaineyDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-4889-8783
Broad Institute · USTufts University · USMassachusetts Institute of Technology · US

Funding

Predicting the emergence of antibiotic resistance through multi-omics approaches and Immune System-surveillanU01AI124302 · NIAID · BOSTON COLLEGE · PI BENTO, JOSE, COOPER, VAUGHN · 2016 to 2020
$10.2M
Drug resistance enablers and their role in antibiotic treatment failureU19AI158076 · NIAID · BROAD INSTITUTE, INC. · PI VAN OPIJNEN, TIM · 2022 to 2025
$10.0M
MOLECULAR ANALYSIS OF MICROBIAL PATHOGENST32AI007422 · NIAID · TUFTS UNIVERSITY BOSTON · PI Ralph R. Isberg · 1992 to 2026
$5.7M
Tri-Institutional PhD Program in Computational Biology & MedicineT32GM132083 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Doron Betel, Iman Hajirasouliha · 2020 to 2026
$3.6M
Designing mammarenavirus live vaccines with unbreachable attenuationR21AI169789 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI DE LA TORRE, JUAN C. · 2022 to 2023
$488k
Identification of the Achilles’ heel in Acinetobacter fluoroquinolone-resistant mutantsR21AI128328 · NIAID · TUFTS UNIVERSITY BOSTON · PI ISBERG, RALPH R. · 2017 to 2018
$454k
NIAID NIH HHS R21 AI128328NIAID NIH HHS R21 AI169789NIAID NIH HHS T32 AI007422NIAID NIH HHS U01 AI124302NIAID NIH HHS U19 AI158076NIGMS NIH HHS T32 GM132083
6 · The paper itself

Abstract

Antibiotic resistance, especially in multidrug-resistant ESKAPE pathogens, remains a worldwide problem. Combination antimicrobial therapies may be an important strategy to overcome resistance and broaden the spectrum of existing antibiotics. However, this strategy is limited by the ability to efficiently screen large combinatorial chemical spaces. Here, we deployed a high-throughput combinatorial screening platform, DropArray, to evaluate the interactions of over 30,000 compounds with up to 22 antibiotics and 6 strains of Gram-negative ESKAPE pathogens, totaling to over 1.3 million unique strain-antibiotic-compound combinations. In this dataset, compounds more frequently exhibited synergy with known antibiotics than single-agent activity. We identified a compound, P2-56, and developed a more potent analog, P2-56-3, which potentiated rifampin (RIF) activity against

Indexed as

Acinetobacter baumanniiantibiotic combinations discoveryantibiotic potentiatorsBiological SciencesGram-negative ESKAPE pathogensMicrobiology

Identifiers

PMID38585790
PMCPMC10996685
OpenAlexW4393230170

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.