Evidence map›Paper›PMID 27325887›Full record

ArticleThe Journal of experimental medicine2016

Identification and treatment of the Staphylococcus aureus reservoir in vivo.

Bas G J Surewaard, Justin F Deniset, Franz J Zemp, Matthias Amrein, Michael Otto, John Conly, Abdelwahab Omri, Robin M Yates, Paul Kubes

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 151 papers.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed
12.7field-weighted citation impact, top 1% 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

151 citing papers in PubMed, 247 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Bas G J SurewaardSnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Medical Microbiology, University Medical Centre, 3584 CX Utrecht, the Netherlands.
Justin F DenisetSnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
Franz J ZempSnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
Matthias AmreinDepartment of Cell Biology and Anatomy, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
Michael OttoPathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
John ConlySnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Pathology and Laboratory Medicine, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Microbiology, Infectious Diseases and Immunology, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
Abdelwahab OmriDepartment of Chemistry and Biochemistry, Laurentian University, Sudbury ON P3E 2C6, Ontario, Canada.
Robin M YatesSnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
Paul KubesSnyder Institute for Chronic Diseases, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada Department of Physiology and Pharmacology, University of Calgary, Calgary AB T2N 1N4, Alberta, Canada.
University of Calgary · CALaurentian University · CANational Institute of Allergy and Infectious Diseases · US

Funding

Staphylococcal pathogenesisZIAAI000904 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI OTTO, MICHAEL · 2009 to 2025
$22.6M
CIHR
6 · The paper itself

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is reaching epidemic proportions causing morbidity, mortality, and chronic disease due to relapses, suggesting an intracellular reservoir. Using spinning-disk confocal intravital microscopy to track MRSA-GFP in vivo, we identified that within minutes after intravenous infection MRSA is primarily sequestered and killed by intravascular Kupffer cells (KCs) in the liver. However, a minority of the Staphylococci overcome the KC's antimicrobial defenses. These bacteria survive and proliferate for many days within this intracellular niche, where they remain undetected by recruited neutrophils. Over time, the KCs lyse, releasing bacteria into the circulation, enabling dissemination to other organs such as the kidneys. Vancomycin, the antibiotic of choice to treat MRSA bacteremia, could not penetrate the KCs to eradicate intracellular MRSA. However, based on the intravascular location of these specific macrophages, we designed a liposomal formulation of vancomycin that is efficiently taken up by KCs and diminished the intracellular MRSA. Targeting the source of the reservoir dramatically protected the liver but also dissemination to other organs, and prevented mortality. This vancomycin formulation strategy could help treat patients with Staphylococcal bacteremia without a need for novel antibiotics by targeting the previously inaccessible intracellular reservoir in KCs.

Indexed as

AnimalsBacteremiaKupffer CellsMaleMethicillin-Resistant Staphylococcus aureusMiceMice, KnockoutNeutrophilsStaphylococcal Infections

Identifiers

PMID27325887
PMCPMC4925027
OpenAlexW2440341397

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.