Evidence map›Paper›PMID 26869441›Full record

ArticleJournal of pharmaceutical sciences2016

Quantitation of Polymyxin-Lipopolysaccharide Interactions Using an Image-Based Fluorescent Probe.

Mitchell P McInerney, Kade D Roberts, Philip E Thompson, Jian Li, Roger L Nation, Tony Velkov, Joseph A Nicolazzo

Open access · bronzeAbstract read
In one paragraph

Article in Journal of pharmaceutical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
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  6. The Attenuated Protective Effect of Outer Membrane Vesicles Produced by aFrontiers in cellular and infection microbiology · 2021
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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

7 authors at 1 institution in 1 country.

Mitchell P McInerneyDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Kade D RobertsMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Philip E ThompsonMedicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Jian LiDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Roger L NationDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Tony VelkovDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Joseph A NicolazzoDrug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. Electronic address: joseph.nicolazzo@monash.edu.
Monash University · AU

Funding

New Tricks for 'Old' Drugs: PK/PD of Polymyxin Nonantibiotic CombinationsR01AI111965 · NIAID · MONASH UNIVERSITY · PI LI, JIAN · 2014 to 2018
$4.3M
Targeting superbugs: discovery and development of new broad-spectrum lipopeptidesR01AI098771 · NIAID · MONASH UNIVERSITY · PI LI, JIAN · 2012 to 2016
$4.3M
NIAID NIH HHS R01 AI098771NIAID NIH HHS R01 AI111965
6 · The paper itself

Abstract

The frequency of polymyxin-resistant pathogenic Gram-negative bacteria appearing in the clinic is increasing, and the consequences are largely mediated by modification of lipopolysaccharide (LPS) in the outer membrane. As polymyxins exert their antibacterial effect by binding to LPS, understanding their mode of binding will prove highly valuable for new antibiotic discovery. In this study, we assess the potential of MIPS-9451, a fluorescent polymyxin analogue designed for imaging studies, as a fluorescent reporter molecule, titrating it against 17 different Gram-negative species and/or strains of LPS. MIPS-9451 bound to the various species and/or strains of LPS with a dissociation constant ranging between 0.14 ± 0.01 μM (Escherichia coli) and 0.90 ± 0.42 μM (Porphyromonas gingivalis; mean ± standard error). Furthermore, we assessed the applicability of MIPS-9451 to rank affinities of polymyxin B to different LPS species in a displacement assay which yielded inhibition constants of 6.2 μM ± 33%, 7.2 μM ± 30%, and 0.95 μM ± 13% for Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella enterica, respectively (mean ± coefficient of variation). The results from this study are concordant with those observed with similarly structured polymyxin probes, confirming the potential of MIPS-9451 for quantitation of polymyxin-LPS affinities in discovery programs of novel polymyxin antibiotics.

Indexed as

Anti-Bacterial AgentsDrug InteractionsFluorescent DyesHumansKlebsiella pneumoniaeLipopolysaccharidesPolymyxinsProtein BindingPseudomonas aeruginosaAnti-Bacterial AgentsFluorescent DyesLipopolysaccharidesPolymyxinsanti-infectivesdrug resistancefluorescence spectroscopyin vitro modelspeptidesstructure–activity relationship

Identifiers

PMID26869441
PMCPMC5149457
OpenAlexW2233935247

What OpenQuestion holds

Textmetadata
LicenceTDM
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.