Evidence map›Paper›PMID 41198856›Full record

ArticleCommunications biology2025

Unraveling the mechanisms behind the enhanced efficacy of β-lactam-based sideromycins.

Evelyne Lacasse, Renaud Binette, Héloïse Guibout, Riu Liu, Yun-Ming Lin, Manuka Ghosh, Pierre-Luc Boudreault, Marvin J Miller, François Malouin

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Evelyne LacasseDépartement de biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.ORCID http://orcid.org/0009-0004-7217-3768
Renaud BinetteDépartement de chimie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Héloïse GuiboutDépartement de biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
Riu LiuHsiri Therapeutics, Media, PA, USA.
Yun-Ming LinHsiri Therapeutics, Media, PA, USA.
Manuka GhoshHsiri Therapeutics, Media, PA, USA.
Pierre-Luc BoudreaultDépartement de Pharmacologie-Physiologie, Institut de Pharmacologie de Sherbrooke, Faculté de Médecine et des Sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.ORCID http://orcid.org/0000-0002-2032-7970
Marvin J MillerHsiri Therapeutics, Media, PA, USA. mmiller1@nd.edu.ORCID http://orcid.org/0000-0002-3704-8214
François MalouinDépartement de biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. francois.malouin@usherbrooke.ca.ORCID http://orcid.org/0000-0001-5031-345X

Funding

Fonds de Recherche du Québec - Nature et Technologies (Quebec Fund for Research in Nature and Technology) 2019-PR-255463Fonds de Recherche du Québec - Nature et Technologies (Quebec Fund for Research in Nature and Technology) https://doi.org/10.69777/334786Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) 2020-04811Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) BESD3-556674-2020
6 · The paper itself

Abstract

Previous studies have explored combining β-lactams with siderophores to create Trojan horse molecules that can penetrate the outer membrane of Gram-negative bacteria via TonB-dependent transporter (TBDT). While the main advantage explaining their enhanced antibiotic activity is believed to be improved membrane permeability, other factors remain underexplored. This study evaluates three siderophore-β-lactam compounds: a bis-catechol siderophore linked to ampicillin or loracarbef, and a mixed bis-catechol-mono-hydroxamate siderophore linked to cefaclor. Minimal inhibitory concentrations showed that siderophore conjugation could enhance β-lactam efficacy by over 8000-fold. Comparison with unconjugated β-lactams revealed a complex interplay between β-lactamase susceptibility, competition with endogenous siderophore, membrane uptake, and binding to penicillin-binding proteins (PBPs). Enhanced PBP binding, particularly in Escherichia coli, emerged as a key factor contributing to improved bacterial inhibition by siderophore-β-lactam conjugates. Overall, the study provides insights into how siderophore conjugation enhances β-lactam activity and the therapeutic potential of the conjugates as narrow or broad-spectrum antibiotics.

Indexed as

Anti-Bacterial Agentsbeta-LactamsSiderophoresEscherichia coliFerrous CompoundsMicrobial Sensitivity TestsPenicillin-Binding ProteinsPeptidesAnti-Bacterial Agentsbeta-LactamsFerrous CompoundsPenicillin-Binding ProteinsPeptidessideromycinsSiderophores

Identifiers

PMID41198856
PMCPMC12592502

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.