Evidence map›Paper›PMID 25495032›Full record

ArticleJournal of the American Chemical Society2015

Catalytic spectrum of the penicillin-binding protein 4 of Pseudomonas aeruginosa, a nexus for the induction of β-lactam antibiotic resistance.

Mijoon Lee, Dusan Hesek, Blas Blázquez, Elena Lastochkin, Bill Boggess, Jed F Fisher, Shahriar Mobashery

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.5field-weighted citation impact, top 21% 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

24 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Microbiology spectrum · 2023
    Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. β-lactam Resistance inPathogens (Basel, Switzerland) · 2021
    Review
  12. Detection of Carbapenem-Resistance Genes inAntibiotics (Basel, Switzerland) · 2020
    Article
  13. Article
  14. Constructing and deconstructing the bacterial cell wall.Protein science : a publication of the Protein Society · 2020
    Review
  15. Article
  16. Review
  17. Article
  18. Frontiers in microbiology · 2017
    Review
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Mijoon LeeDepartment of Chemistry and Biochemistry, University of Notre Dame , Notre Dame, Indiana 46556, United States.
Dusan Hesek
Blas Blázquez
Elena Lastochkin
Bill Boggess
Jed F Fisher
Shahriar Mobashery
University of Notre Dame · US

Funding

Penicillin-Binding Proteins, Mechanism and InhibitionR01GM061629 · NIGMS · WAYNE STATE UNIVERSITY · PI MOBASHERY, SHAHRIAR · 2001 to 2018
$5.1M
NIGMS NIH HHS GM61629NIGMS NIH HHS R01 GM061629
6 · The paper itself

Abstract

Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen. A primary contributor to its ability to resist β-lactam antibiotics is the expression, following detection of the β-lactam, of the AmpC β-lactamase. As AmpC expression is directly linked to the recycling of the peptidoglycan of the bacterial cell wall, an important question is the identity of the signaling molecule(s) in this relationship. One mechanism used by clinical strains to elevate AmpC expression is loss of function of penicillin-binding protein 4 (PBP4). As the mechanism of the β-lactams is PBP inactivation, this result implies that the loss of the catalytic function of PBP4 ultimately leads to induction of antibiotic resistance. PBP4 is a bifunctional enzyme having both dd-carboxypeptidase and endopeptidase activities. Substrates for both the dd-carboxypeptidase and the 4,3-endopeptidase activities were prepared by multistep synthesis, and their turnover competence with respect to PBP4 was evaluated. The endopeptidase activity is specific to hydrolysis of 4,3-cross-linked peptidoglycan. PBP4 catalyzes both reactions equally well. When P. aeruginosa is grown in the presence of a strong inducer of AmpC, the quantities of both the stem pentapeptide (the substrate for the dd-carboxypeptidase activity) and the 4,3-cross-linked peptidoglycan (the substrate for the 4,3-endopeptidase activity) increase. In the presence of β-lactam antibiotics these altered cell-wall segments enter into the muropeptide recycling pathway, the conduit connecting the sensing event in the periplasm and the unleashing of resistance mechanisms in the cytoplasm.

Indexed as

Anti-Bacterial Agentsbeta-Lactam ResistanceBiocatalysisMolecular ConformationPenicillin-Binding ProteinsPseudomonas aeruginosaAnti-Bacterial AgentsPenicillin-Binding Proteins

Identifiers

PMID25495032
PMCPMC4304477
OpenAlexW1963716010

What OpenQuestion holds

Textmetadata
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.