Evidence map›Paper›PMID 39843773›Full record

Articlenpj antimicrobials and resistance2023

Di-berberine conjugates as chemical probes of Pseudomonas aeruginosa MexXY-OprM efflux function and inhibition.

Logan G Kavanaugh, Andrew R Mahoney, Debayan Dey, William M Wuest, Graeme L Conn

Abstract read
In one paragraph

Article in npj antimicrobials and resistance, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Discovery of Novel Molecular Scaffolds to OvercomeInternational journal of molecular sciences · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Regulation, structure, and activity of theAntimicrobial agents and chemotherapy · 2025
    Review
  8. Determination ofMicrobiology spectrum · 2025
    Article
  9. Determination ofbioRxiv : the preprint server for biology · 2024
    Article
  10. Review
  11. Review
  12. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Logan G Kavanaugh *Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
Andrew R Mahoney *Department of Chemistry, Emory University, Atlanta, GA, USA.
Debayan DeyDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
William M WuestDepartment of Chemistry, Emory University, Atlanta, GA, USA. wwuest@emory.edu.
Graeme L ConnDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA. gconn@emory.edu.ORCID http://orcid.org/0000-0002-2419-380X

Funding

Natural Product-Inspired Approaches Toward The Development Of Antivirulence And Species-Specific InhibitorsR35GM119426 · NIGMS · TEMPLE UNIV OF THE COMMONWEALTH · PI William M Wuest · 2016 to 2026
$4.8M
Molecular basis for substrate discrimination by transporter protein MexY of the MexXY-OprM efflux pump in Pseudomonas aeruginosaF31GM143891 · NIGMS · EMORY UNIVERSITY · PI KAVANAUGH, LOGAN GLENN · 2021 to 2024
$165k
Cystic Fibrosis Foundation (CF Foundation) Kavana21H0NIGMS NIH HHS F31 GM143891NIGMS NIH HHS R35 GM119426
6 · The paper itself

Abstract

The Resistance-Nodulation-Division (RND) efflux pump superfamily is pervasive among Gram-negative pathogens and contributes extensively to clinical antibiotic resistance. The opportunistic pathogen Pseudomonas aeruginosa contains 12 RND-type efflux systems, with four contributing to resistance including MexXY-OprM which is uniquely able to export aminoglycosides. At the site of initial substrate recognition, small molecule probes of the inner membrane transporter (e.g., MexY) have potential as important functional tools to understand substrate selectivity and a foundation for developing adjuvant efflux pump inhibitors (EPIs). Here, we optimized the scaffold of berberine, a known but weak MexY EPI, using an in-silico high-throughput screen to identify di-berberine conjugates with enhanced synergistic action with aminoglycosides. Further, docking and molecular dynamics simulations of di-berberine conjugates reveal unique contact residues and thus sensitivities of MexY from distinct P. aeruginosa strains. This work thereby reveals di-berberine conjugates to be useful probes of MexY transporter function and potential leads for EPI development.

Identifiers

PMID39843773
PMCPMC11721654

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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.