Evidence map›Paper›PMID 26248337›Full record

ArticleCellular microbiology2016

Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages.

Jamil Jubrail, Paul Morris, Martin A Bewley, Simon Stoneham, Simon A Johnston, Simon J Foster, Andrew A Peden, Robert C Read, Helen M Marriott, David H Dockrell

Open access · hybridAbstract read
In one paragraph

Article in Cellular microbiology, 2016. 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
4.1field-weighted citation impact, top 6% 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, 118 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. The Complex Intracellular Lifecycle ofInternational journal of molecular sciences · 2024
    Review
  12. Article
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  18. Article
  19. Article
  20. Innovations in Evaluating Statin Benefit and Efficacy inInternational journal of molecular sciences · 2022
    Review

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

10 authors at 3 institutions in 1 country.

Jamil JubrailDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
Paul MorrisDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
Martin A BewleyDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
Simon StonehamDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
Simon A JohnstonDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
Simon J FosterThe Florey Institute, University of Sheffield, Sheffield, UK.
Andrew A PedenDepartment of Biomedical Sciences, University of Sheffield, Sheffield, UK.
Robert C ReadAcademic Unit of Clinical and Experimental Sciences, University of Southampton Medical School, Southampton, UK.
Helen M MarriottDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
David H DockrellDepartment of Infection and Immunity, University of Sheffield, Sheffield, UK.
University of Sheffield · GBSheffield Teaching Hospitals NHS Foundation Trust · GBUniversity of Southampton · GB

Funding

Biotechnology and Biological Sciences Research Council BB/L002841/1Medical Research Council G0902354Medical Research Council MR/J009156/1
6 · The paper itself

Abstract

Macrophages are critical effectors of the early innate response to bacteria in tissues. Phagocytosis and killing of bacteria are interrelated functions essential for bacterial clearance but the rate-limiting step when macrophages are challenged with large numbers of the major medical pathogen Staphylococcus aureus is unknown. We show that macrophages have a finite capacity for intracellular killing and fail to match sustained phagocytosis with sustained microbial killing when exposed to large inocula of S. aureus (Newman, SH1000 and USA300 strains). S. aureus ingestion by macrophages is associated with a rapid decline in bacterial viability immediately after phagocytosis. However, not all bacteria are killed in the phagolysosome, and we demonstrate reduced acidification of the phagolysosome, associated with failure of phagolysosomal maturation and reduced activation of cathepsin D. This results in accumulation of viable intracellular bacteria in macrophages. We show macrophages fail to engage apoptosis-associated bacterial killing. Ultittop mately macrophages with viable bacteria undergo cell lysis, and viable bacteria are released and can be internalized by other macrophages. We show that cycles of lysis and reuptake maintain a pool of viable intracellular bacteria over time when killing is overwhelmed and demonstrate intracellular persistence in alveolar macrophages in the lungs in a murine model.

Indexed as

Microbial ViabilityPhagocytosisAnimalsCell SurvivalDisease Models, AnimalMacrophagesMicePneumonia, StaphylococcalStaphylococcus aureusantimicrobialimmunologymicrobial-cell interactionStaphylococci

Identifiers

PMID26248337
PMCPMC4778410
OpenAlexW1920153897

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.