Evidence map›Paper›PMID 23733461›Full record

ArticleAntimicrobial agents and chemotherapy2013

Antibiotic trapping by plasmid-encoded CMY-2 β-lactamase combined with reduced outer membrane permeability as a mechanism of carbapenem resistance in Escherichia coli.

Wil H F Goessens, Akke K van der Bij, Ria van Boxtel, Johann D D Pitout, Peter van Ulsen, Damian C Melles, Jan Tommassen

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.2field-weighted citation impact, top 25% 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

35 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Clinical carbapenem-resistantMicrobiology spectrum · 2025
    Article
  6. Proteogenomic analysis demonstrates increasedAntimicrobial agents and chemotherapy · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Insight into the Mechanisms of Carbapenem Resistance inAntibiotics (Basel, Switzerland) · 2023
    Article
  12. Article
  13. Article
  14. Class C β-Lactamases: Molecular Characteristics.Clinical microbiology reviews · 2022
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Present and Future of Carbapenem-resistantAntibiotics (Basel, Switzerland) · 2019
    Review
  20. 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

7 authors at 4 institutions in 2 countries.

Wil H F GoessensDepartment of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands. w.goessens@erasmusmc.nl
Akke K van der Bij
Ria van Boxtel
Johann D D Pitout
Peter van Ulsen
Damian C Melles
Jan Tommassen
Erasmus MC · NLUtrecht University · NLUniversity of Calgary · CAVrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A liver transplant patient was admitted with cholangitis, for which meropenem therapy was started. Initial cultures showed a carbapenem-susceptible (CS) Escherichia coli strain, but during admission, a carbapenem-resistant (CR) E. coli strain was isolated. Analysis of the outer membrane protein profiles showed that both CS and CR E. coli lacked the porins OmpF and OmpC. Furthermore, PCR and sequence analysis revealed that both CS and CR E. coli possessed bla(CTX-M-15) and bla(OXA-1). The CR E. coli strain additionally harbored bla(CMY-2) and demonstrated a >15-fold increase in β-lactamase activity against nitrocefin, but no hydrolysis of meropenem was detected. However, nitrocefin hydrolysis appeared strongly inhibited by meropenem. Furthermore, the CMY-2 enzyme demonstrated lower electrophoretic mobility after its incubation either in vitro or in vivo with meropenem, indicative of its covalent modification with meropenem. The presence of the acyl-enzyme complex was confirmed by mass spectrometry. By transformation of the CMY-2-encoding plasmid into various E. coli strains, it was established that both porin deficiency and high-level expression of the enzyme were needed to confer meropenem resistance. In conclusion, carbapenem resistance emerged by a combination of elevated β-lactamase production and lack of porin expression. Due to the reduced outer membrane permeability, only small amounts of meropenem can enter the periplasm, where they are trapped but not degraded by the large amount of the β-lactamase. This study, therefore, provides evidence that the mechanism of "trapping" by CMY-2 β-lactamase plays a role in carbapenem resistance.

Indexed as

Cell Membrane PermeabilityAnti-Bacterial AgentsBacterial Outer Membrane Proteinsbeta-LactamasesCephalosporinsDrug Resistance, Multiple, BacterialEnzyme ActivationEscherichia coliEscherichia coli InfectionsEscherichia coli ProteinsFemaleHumansHydrolysisMeropenemMicrobial Sensitivity TestsPeriplasmAnti-Bacterial AgentsBacterial Outer Membrane Proteinsbeta-lactamase CMY-2beta-lactamase CTX-M-15beta-lactamase OXA-2beta-LactamasesCephalosporinsEscherichia coli ProteinsMeropenemnitrocefinThienamycins

Identifiers

PMID23733461
PMCPMC3719783
OpenAlexW1975501206

What OpenQuestion holds

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Registered trials

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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.