Evidence map›Paper›PMID 31877796›Full record

ArticleMicroorganisms2019

Biochemical and Structural Characterization of OXA-405, an OXA-48 Variant with Extended-Spectrum β-Lactamase Activity.

Saoussen Oueslati, Pascal Retailleau, Ludovic Marchini, Laurent Dortet, Rémy A Bonnin, Bogdan I Iorga, Thierry Naas

Abstract read
In one paragraph

Article in Microorganisms, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Detection of OXA-48 Gene in Carbapenem-ResistantInfection and drug resistance · 2020
    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.

Saoussen OueslatiEA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Faculty of Medicine of Paris-Sud University, Labex LERMIT, University Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.
Pascal RetailleauInstitut de Chimie des Substances Naturelles, CNRS UPR 2301, Labex LERMIT, 91198 Gif-sur-Yvettte, France.
Ludovic MarchiniInstitut de Chimie des Substances Naturelles, CNRS UPR 2301, Labex LERMIT, 91198 Gif-sur-Yvettte, France.
Laurent DortetEA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Faculty of Medicine of Paris-Sud University, Labex LERMIT, University Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.
Rémy A BonninEA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Faculty of Medicine of Paris-Sud University, Labex LERMIT, University Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.ORCID 0000-0002-2307-3232
Bogdan I IorgaInstitut de Chimie des Substances Naturelles, CNRS UPR 2301, Labex LERMIT, 91198 Gif-sur-Yvettte, France.ORCID 0000-0003-0392-1350
Thierry NaasEA7361 "Structure, dynamic, function and expression of broad spectrum β-lactamases", Faculty of Medicine of Paris-Sud University, Labex LERMIT, University Paris-Saclay, 94270 Le Kremlin-Bicêtre, France.ORCID 0000-0001-9937-9572

Funding

Agence Nationale de la Recherche ANR-10-LABX-33Agence Nationale de la Recherche ANR-14-JAMR-0002Assistance publique-Hôpitaux de Paris CHU BicêtreUniversité Paris-Sud EA7361
6 · The paper itself

Abstract

OXA-48-producing Enterobacterales have now widely disseminated globally. A sign of their extensive spread is the identification of an increasing number of OXA-48 variants. Among them, three are particularly interesting, OXA-163, OXA-247 and OXA-405, since they have lost carbapenem activities and gained expanded-spectrum cephalosporin hydrolytic activity subsequent to a four amino-acid (AA) deletion in the β5-β6 loop. We investigated the mechanisms responsible for substrate specificity of OXA-405. Kinetic parameters confirmed that OXA-405 has a hydrolytic profile compatible with an ESBL (hydrolysis of expanded spectrum cephalosporins and susceptibility to class A inhibitors). Molecular modeling techniques and 3D structure determination show that the overall dimeric structure of OXA-405 is very similar to that of OXA-48, except for the β5-β6 loop, which is shorter for OXA-405, suggesting that the length of the β5-β6 loop is critical for substrate specificity. Covalent docking with selected substrates and molecular dynamics simulations evidenced the structural changes induced by substrate binding, as well as the distribution of water molecules in the active site and their role in substrate hydrolysis. All this data may represent the structural basis for the design of new and efficient class D inhibitors.

Indexed as

antibiotic resistancebeta-lactamasecarbapenemasecrystal structuredockingoxacillinaseOXA-ESBLsubstrate selectivity

Identifiers

PMID31877796
PMCPMC7022249

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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.