Evidence map›Paper›PMID 25779578›Full record

ArticleAntimicrobial agents and chemotherapy2015

A novel gene amplification causes upregulation of the PatAB ABC transporter and fluoroquinolone resistance in Streptococcus pneumoniae.

Alison J Baylay, Alasdair Ivens, Laura J V Piddock

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.9field-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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Antibiotic resistance mediated by gene amplifications.npj antimicrobials and resistance · 2024
    Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Comparative Genomic Analysis ofFrontiers in microbiology · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. 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

3 authors at 2 institutions in 1 country.

Alison J BaylayAntimicrobials Research Group, School of Immunity and Infection, Institute of Microbiology and Infection, and College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Alasdair IvensCentre for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
Laura J V PiddockAntimicrobials Research Group, School of Immunity and Infection, Institute of Microbiology and Infection, and College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom l.j.v.piddock@bham.ac.uk.
University of Birmingham · GBCentre for Immunity, Infection and Evolution · GB

Funding

Wellcome Trust 095831
6 · The paper itself

Abstract

Overexpression of the ABC transporter genes patA and patB confers efflux-mediated fluoroquinolone resistance in Streptococcus pneumoniae and is also linked to pneumococcal stress responses. Although upregulation of patAB has been observed in many laboratory mutants and clinical isolates, the regulatory mechanisms controlling expression of these genes are unknown. In this study, we aimed to identify the cause of high-level constitutive overexpression of patAB in M184, a multidrug-resistant mutant of S. pneumoniae R6. Using a whole-genome transformation and sequencing approach, we identified a novel duplication of a 9.2-kb region of the M184 genome which included the patAB genes. This duplication did not affect growth and was semistable with a low segregation rate. The expression levels of patAB in M184 were much higher than those that could be fully explained by doubling of the gene dosage alone, and inactivation of the first copy of patA had no effect on multidrug resistance. Using a green fluorescent protein reporter system, increased patAB expression was ascribed to transcriptional read-through from a tRNA gene upstream of the second copy of patAB. This is the first report of a large genomic duplication causing antibiotic resistance in S. pneumoniae and also of a genomic duplication causing antibiotic resistance by a promoter switching mechanism.

Indexed as

Anti-Bacterial AgentsATP-Binding Cassette TransportersBacterial ProteinsFluoroquinolonesGene AmplificationStreptococcus pneumoniaeAnti-Bacterial AgentsATP-Binding Cassette TransportersBacterial ProteinsFluoroquinolones

Identifiers

PMID25779578
PMCPMC4432121
OpenAlexW2112889044

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.