Evidence map›Paper›PMID 30462485›Full record

ArticleACS synthetic biology2018

Genomic Deoxyxylulose Phosphate Reductoisomerase (DXR) Mutations Conferring Resistance to the Antimalarial Drug Fosmidomycin in E. coli.

Gur Pines, Eun Joong Oh, Marcelo C Bassalo, Alaksh Choudhury, Andrew D Garst, Reilly G Fankhauser, Carrie A Eckert, Ryan T Gill

Open access · greenAbstract read
In one paragraph

Article in ACS synthetic biology, 2018. 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
1.4field-weighted citation impact, top 17% 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, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Mutational fitness landscape and drug resistance.Current opinion in structural biology · 2023
    Review
  5. Article
  6. Highly efficient libraries design for saturation mutagenesis.Synthetic biology (Oxford, England) · 2022
    Article
  7. Article
  8. Article
  9. Review
  10. Article
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

8 authors at 2 institutions in 1 country.

Gur PinesRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.ORCID 0000-0002-1757-6722
Eun Joong OhRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.ORCID 0000-0001-7145-0752
Marcelo C BassaloRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.
Alaksh ChoudhuryDepartment of Chemical and Biological Engineering , University of Colorado Boulder , 596 UCB , Boulder , Colorado 80309 , United States.
Andrew D GarstRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.
Reilly G FankhauserRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.ORCID 0000-0001-6318-4255
Carrie A EckertRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.ORCID 0000-0003-4201-2926
Ryan T GillRenewable and Sustainable Energy Institute , University of Colorado Boulder , 027 UCB , Boulder , Colorado 80309 , United States.ORCID 0000-0003-2062-303X
University of Colorado Boulder · USNational Laboratory of the Rockies · US

Funding

Multiplex sequence to activity mapping at the pathway scaleR21AI128296 · NIAID · UNIVERSITY OF COLORADO · PI GILL, RYAN T · 2017 to 2018
$424k
NIAID NIH HHS R21 AI128296
6 · The paper itself

Abstract

Sequence to activity mapping technologies are rapidly developing, enabling the generation and isolation of mutations conferring novel phenotypes. Here we used the CRISPR enabled trackable genome engineering (CREATE) technology to investigate the inhibition of the essential ispC gene in its native genomic context in Escherichia coli. We created a full saturation library of 33 sites proximal to the ligand binding pocket and challenged this library with the antimalarial drug fosmidomycin, which targets the ispC gene product, DXR. This selection is especially challenging since it is relatively weak in E. coli, with multiple naturally occurring pathways for resistance. We identified several previously unreported mutations that confer fosmidomycin resistance, in highly conserved sites that also exist in pathogens including the malaria-inducing Plasmodium falciparum. This approach may have implications for the isolation of resistance-conferring mutations and may affect the design of future generations of fosmidomycin-based drugs.

Indexed as

Aldose-Ketose IsomerasesAntimalarialsClustered Regularly Interspaced Short Palindromic RepeatsDrug ResistanceEscherichia coliFosfomycinGenetic EngineeringMutationPlasmidsPlasmodium falciparum1-deoxy-D-xylulose 5-phosphate reductoisomeraseAldose-Ketose IsomerasesAntimalarialsFosfomycinfosmidomycinacquired resistanceCRISPR/Cas9deoxyxylulose phosphate reductoisomerasefosmidomycinmalariasequence to activity mapping

Identifiers

PMID30462485
PMCPMC6928208
OpenAlexW2901188527

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.