Evidence map›Paper›PMID 24867990›Full record

ArticleAntimicrobial agents and chemotherapy2014

β-Lactam resistance in methicillin-resistant Staphylococcus aureus USA300 is increased by inactivation of the ClpXP protease.

Kristoffer T Bæk, Angelika Gründling, René G Mogensen, Louise Thøgersen, Andreas Petersen, Wilhelm Paulander, Dorte Frees

Open access · bronzeAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% 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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

  1. Pooled it
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  5. Mutation of lipoprotein processing pathway geneAntimicrobial agents and chemotherapy · 2026
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  7. Methicillin-resistantiScience · 2026
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  16. Review
  17. Machine learning assisted identification of antibiotic-resistantMicrochemical journal : devoted to the application of microtechniques in all branches of science · 2024
    Article
  18. In Vivo Effect of Halicin on Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2024
    Article
  19. Article
  20. Article

11 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Kristoffer T BækFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
Angelika GründlingSection of Microbiology and MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom.
René G MogensenFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
Louise ThøgersenFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
Andreas PetersenStatens Serum Institut, Copenhagen, Denmark.
Wilhelm PaulanderFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark.
Dorte FreesFaculty of Health and Medical Sciences, Department of Veterinary Disease Biology, University of Copenhagen, Frederiksberg, Denmark df@sund.ku.dk.
University of Copenhagen · DKImperial College London · GBStatens Serum Institut · DK

Funding

European Research Council 260371Medical Research Council MR/J006874/1
6 · The paper itself

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has acquired the mecA gene encoding a peptidoglycan transpeptidase, penicillin binding protein 2a (PBP2a), which has decreased affinity for β-lactams. Quickly spreading and highly virulent community-acquired (CA) MRSA strains recently emerged as a frequent cause of infection in individuals without exposure to the health care system. In this study, we found that the inactivation of the components of the ClpXP protease substantially increased the β-lactam resistance level of a CA-MRSA USA300 strain, suggesting that the proteolytic activity of ClpXP controls one or more pathways modulating β-lactam resistance. These pathways do not involve the control of mecA expression, as the cellular levels of PBP2a were unaltered in the clp mutants. An analysis of the cell envelope properties of the clpX and clpP mutants revealed a number of distinct phenotypes that may contribute to the enhanced β-lactam tolerance. Both mutants displayed significantly thicker cell walls, increased peptidoglycan cross-linking, and altered composition of monomeric muropeptide species compared to those of the wild types. Moreover, changes in Sle1-mediated peptidoglycan hydrolysis and altered processing of the major autolysin Atl were observed in the clp mutants. In conclusion, the results presented here point to an important role for the ClpXP protease in controlling cell wall metabolism and add novel insights into the molecular factors that determine strain-dependent β-lactam resistance.

Indexed as

Gene Expression Regulation, BacterialAnti-Bacterial AgentsBacterial Proteinsbeta-Lactam Resistancebeta-LactamsCell WallEndopeptidase ClpIsoenzymesMetabolic Networks and PathwaysMethicillin-Resistant Staphylococcus aureusMutationN-Acetylmuramoyl-L-alanine AmidasePenicillin-Binding ProteinsPeptidoglycanAnti-Bacterial AgentsBacterial Proteinsbeta-LactamsEndopeptidase ClpIsoenzymesmecA protein, Staphylococcus aureusN-Acetylmuramoyl-L-alanine AmidasePenicillin-Binding ProteinsPeptidoglycan

Identifiers

PMID24867990
PMCPMC4136064
OpenAlexW2109093365

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.