Evidence map›Paper›PMID 32240953›Full record

ArticleiScience2020

A Strategic Target Rescues Trimethoprim Sensitivity in Escherichia coli.

Amrisha Bhosle, Akshay Datey, Giridhar Chandrasekharan, Deepshikha Singh, Dipshikha Chakravortty, Nagasuma Chandra

Open access · goldAbstract read
In one paragraph

Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.2field-weighted citation impact, top 13% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Antibiotic resistance ofOpen veterinary journal · 2025
    Article
  3. Review
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  5. Article
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  7. Article
  8. Article
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  10. Article
  11. Article
  12. Article
  13. Immune Subtyping in Latent Tuberculosis.Frontiers in immunology · 2021
    Article
  14. Article
  15. 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

6 authors at 1 institution in 1 country.

Amrisha BhosleDepartment of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India.
Akshay DateyCenter for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka 560012, India.
Giridhar ChandrasekharanDepartment of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India.
Deepshikha SinghDepartment of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India.
Dipshikha ChakravorttyCenter for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka 560012, India; Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, Karnataka 560012, India. Electronic address: dipa@iisc.ac.in.
Nagasuma ChandraDepartment of Biochemistry, Indian Institute of Science, Bangalore, Karnataka 560012, India; Center for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka 560012, India. Electronic address: nchandra@iisc.ac.in.
Indian Institute of Science Bangalore · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Trimethoprim, a preferred treatment for urinary tract infections, is becoming obsolete owing to the rapid dissemination of resistant E. coli. Although direct resistance mechanisms such as overexpression of a mutant FolA and dfr enzymes are well characterized, associated alterations that drive or sustain resistance are unknown. We identify the repertoire of resistance-associated perturbations by constructing and interrogating a transcriptome-integrated functional interactome. From the cross talk between perturbations in stress-response and metabolic pathways, we identify the critical dependence on serine hydroxymethyltransferase (GlyA) as an emergent vulnerability. Through its deletion, we demonstrate that GlyA is necessary to sustain high levels of resistance in both laboratory-evolved resistant E. coli and a multidrug-resistant clinical isolate. Through comparative evolution, we show that the absence of GlyA activity decelerates the acquisition of resistance in E. coli. Put together, our results identify GlyA as a promising target, providing a basis for the rational design of drug combinations.

Indexed as

MicrobiologyMulti-Drug Resistant OrganismsTranscriptomics

Identifiers

PMID32240953
PMCPMC7115098
OpenAlexW3010645158

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.