Evidence map›Paper›PMID 37119793›Full record

ArticleTuberculosis (Edinburgh, Scotland)2023

Polyfluorinated salicylic acid analogs do not interfere with siderophore biosynthesis.

Pooja Hegde, Moyosore O Orimoloye, Sachin Sharma, Curtis A Engelhart, Dirk Schnappinger, Courtney C Aldrich

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

Article in Tuberculosis (Edinburgh, Scotland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
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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

6 authors at 2 institutions in 1 country.

Pooja HegdeDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN, 55455, USA.
Moyosore O OrimoloyeDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN, 55455, USA.
Sachin SharmaDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN, 55455, USA.
Curtis A EngelhartDepartment of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10021, USA.
Dirk SchnappingerDepartment of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10021, USA. Electronic address: dis2003@med.cornell.edu.
Courtney C AldrichDepartment of Medicinal Chemistry, University of Minnesota, 308 Harvard Street SE, Minneapolis, MN, 55455, USA. Electronic address: aldri015@umn.edu.
University of Minnesota · USCornell University · US

Funding

Siderophore Inhibitors for Tuberculosis that Block Mycobactin BiosynthesisR01AI136445 · NIAID · UNIVERSITY OF MINNESOTA · PI ALDRICH, COURTNEY C · 2018 to 2022
$3.8M
NIAID NIH HHS R01 AI136445
6 · The paper itself

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is a leading cause of infectious disease mortality. The salicylic acid derived small molecule siderophores known as mycobactins are essential in vivo for iron acquisition of Mtb where iron is restricted in the host. Herein, we synthesize and explore the mechanism of action of polyfluorinated salicylic acid derivates, which were previously reported to possess potent antimycobacterial activity. We hypothesized fluorinated salicylic acid derivates may inhibit mycobactin biosynthesis through initial bioactivation and conversion to downstream metabolites that block late steps in assembly of the mycobactins. Enzymatic studies demonstrated that some of the fluorinated salicylic acid derivatives compounds were readily activated by the bifunctional adenylating enzyme MbtA, responsible for incorporation of salicylic acid into the mycobactin biosynthetic pathway; however, they did not inhibit mycobactin biosynthesis as confirmed by LS-MS/MS using an authentic synthetic mycobactin standard. Further mechanistic analysis of the most active derivative (Sal-4) using an MbtA-overexpressing Mtb strain as well as complementation studies with iron and salicylic acid revealed Sal-4 cannot be antagonized by overexpression of MbtA or through supplementation with iron or salicylic acid. Taken together, our results indicate the observed antimycobacterial activity of polyfluorinated salicylic acid derivative is independent of mycobactin biosynthesis.

Indexed as

Mycobacterium tuberculosisSiderophoresIronSalicylic AcidTandem Mass SpectrometryIronSalicylic AcidSiderophores

Identifiers

PMID37119793
PMCPMC10247463
OpenAlexW4366606536

What OpenQuestion holds

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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.