Evidence map›Paper›PMID 32877437›Full record

ArticlePloS one2020

Potentiating aminoglycoside antibiotics to reduce their toxic side effects.

Christopher R Rosenberg, Xin Fang, Kyle R Allison

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
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

36 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
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  8. ScreeningOpen research Europe · 2025
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  12. Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

3 authors at 2 institutions in 1 country.

Christopher R RosenbergDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, United States of America.
Xin FangDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, United States of America.
Kyle R AllisonDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, United States of America.ORCID 0000-0003-3960-527X
Georgia Institute of Technology · USColumbia University Irving Medical Center · US

Funding

Isolation and Systems-Level Characterization of Persistent BacteriaDP5OD019792 · OD · EMORY UNIVERSITY · PI ALLISON, KYLE ROUSE · 2014 to 2018
$2.0M
NIH HHS DP5 OD019792
6 · The paper itself

Abstract

The lack of new antibiotics necessitates the improvement of existing ones, many of which are limited by toxic side effects. Aminoglycosides, antibiotics with excellent activity and low bacterial resistance, are hampered by dose-dependent toxic effects in patients (nephrotoxicity, ototoxicity). High antibiotic concentrations are often required to treat dormant, non-dividing bacteria, though previous studies show that aminoglycosides can be activated against such bacteria by specific metabolites. Here, we employed this mechanism to greatly boost the activity of low concentrations of aminoglycosides against prevalent Gram-negative pathogens (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae), suggesting that less toxic drug concentrations might be used effectively in patients. We go on to show that this effect improved treatment of biofilms, did not increase aminoglycoside resistance, and was due to the generation of proton-motive force (PMF). By single-cell microscopy, we demonstrate that stationary-phase cells, while non-dividing, actively maintain a growth-arrested state that is not reversed by metabolite addition. Surprisingly, within starved populations, we observed rare cells (3%) that divided without added nutrients. Additionally, we discovered that mannitol could directly protect human kidney cells from aminoglycoside cytotoxicity, independent of the metabolite's effect on bacteria. This work forwards a mechanism-based strategy to improve existing antibiotics by mitigating their toxic side effects.

Indexed as

AminoglycosidesAnti-Bacterial AgentsBacteriaBacterial InfectionsBiofilmsDrug-Related Side Effects and Adverse ReactionsDrug Resistance, BacterialHumansMicrobial Sensitivity TestsAminoglycosidesAnti-Bacterial Agents

Identifiers

PMID32877437
PMCPMC7467299
OpenAlexW3081936009

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.