Evidence map›Paper›PMID 37460557›Full record

ArticleNature communications2023

Molecular basis of β-lactam antibiotic resistance of ESKAPE bacterium E. faecium Penicillin Binding Protein PBP5.

Yamanappa Hunashal, Ganesan Senthil Kumar, Meng S Choy, Éverton D D'Andréa, Andre Da Silva Santiago, Marta V Schoenle, Charlene Desbonnet, Michel Arthur, Louis B Rice, Rebecca Page and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

30 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  10. Characterization ofVeterinary sciences · 2026
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  11. Review
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  15. Antibiotic Resistance in Dentistry: A Review.Antibiotics (Basel, Switzerland) · 2025
    Review
  16. One health (Amsterdam, Netherlands) · 2025
    Review
  17. Article
  18. Review
  19. Article
  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

11 authors at 5 institutions in 3 countries.

Yamanappa HunashalDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA.
Ganesan Senthil KumarDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA.ORCID 0000-0002-3122-4475
Meng S ChoyDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA.
Éverton D D'AndréaDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
Andre Da Silva SantiagoDepartment of Cell Biology, University of Connecticut Health Center, Farmington, CT, USA.ORCID 0000-0002-3973-3370
Marta V SchoenleDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, USA.
Charlene DesbonnetDepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Michel ArthurINSERM, Sorbonne Université, Université Paris Cité, Paris, France.ORCID 0000-0003-1007-636X
Louis B RiceDepartment of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Rebecca PageDepartment of Cell Biology, University of Connecticut Health Center, Farmington, CT, USA.
Wolfgang PetiDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, CT, USA. peti@uchc.edu.ORCID 0000-0002-8830-6594
UConn Health · USBrown University · USUniversity of Arizona · USInserm · FRNational Institute of Immunology · IN

Funding

Mechanism and activity of beta-lactam resistant enzymes in E. faecium and E. faecalisR01AI141522 · NIAID · RHODE ISLAND HOSPITAL · PI Wolfgang Peti, Louis B. Rice · 2019 to 2026
$5.1M
NIAID NIH HHS R01 AI141522
6 · The paper itself

Abstract

Penicillin-binding proteins (PBPs) are essential for the formation of the bacterial cell wall. They are also the targets of β-lactam antibiotics. In Enterococcus faecium, high levels of resistance to β-lactams are associated with the expression of PBP5, with higher levels of resistance associated with distinct PBP5 variants. To define the molecular mechanism of PBP5-mediated resistance we leveraged biomolecular NMR spectroscopy of PBP5 - due to its size (>70 kDa) a challenging NMR target. Our data show that resistant PBP5 variants show significantly increased dynamics either alone or upon formation of the acyl-enzyme inhibitor complex. Furthermore, these variants also exhibit increased acyl-enzyme hydrolysis. Thus, reducing sidechain bulkiness and expanding surface loops results in increased dynamics that facilitates acyl-enzyme hydrolysis and, via increased β-lactam antibiotic turnover, facilitates β-lactam resistance. Together, these data provide the molecular basis of resistance of clinical E. faecium PBP5 variants, results that are likely applicable to the PBP family.

Indexed as

Anti-Bacterial AgentsHexosyltransferasesBacterial Proteinsbeta-Lactam Resistancebeta-LactamsMicrobial Sensitivity TestsMonobactamsPenicillin-Binding ProteinsAnti-Bacterial AgentsBacterial Proteinsbeta-LactamsHexosyltransferasesMonobactamsPenicillin-Binding Proteins

Identifiers

PMID37460557
PMCPMC10352307
OpenAlexW4384561862

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.