Evidence map›Paper›PMID 26618545›Full record

ArticlePLoS pathogens2015

Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection.

Ching Wen Tseng, Juan Carlos Biancotti, Bethany L Berg, David Gate, Stacey L Kolar, Sabrina Müller, Maria D Rodriguez, Kavon Rezai-Zadeh, Xuemo Fan, David O Beenhouwer and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
3.9field-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

49 citing papers in PubMed, 65 citations in OpenAlex.

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  14. Biomedicines · 2021
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  15. Article
  16. Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021
    Review
  17. Frontiers in immunology · 2021
    Review
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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

12 authors at 3 institutions in 1 country.

Ching Wen TsengDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Juan Carlos BiancottiZilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Bethany L BergDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
David GateZilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
Stacey L KolarDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Sabrina MüllerDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Maria D RodriguezDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Kavon Rezai-ZadehDepartment of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Xuemo FanDepartment of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
David O BeenhouwerDivision of Infectious Diseases, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California; Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, United States of America.
Terrence TownZilkha Neurogenetic Institute, Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
George Y LiuDivision of Pediatric Infectious Diseases and the Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Cedars-Sinai Medical Center · USUniversity of California, Los Angeles · USUniversity of Southern California · US

Funding

Antioxidant-based mechanisms used by staphyloccocus aureus to evade host defensesR01AI074832 · NIAID · CEDARS-SINAI MEDICAL CENTER · PI LIU, GEORGE Y · 2007 to 2010
$1.6M
NIAID NIH HHS R01 AI074832
6 · The paper itself

Abstract

Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL) elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA), exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD)/severe combined immune deficiency (SCID)/IL2rγnull (NSG) mice engrafted with human CD34+ umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL- S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL- S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL- S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor.

Indexed as

Staphylococcus aureusAnimalsBacterial ToxinsDisease Models, AnimalDisease SusceptibilityExotoxinsHumansLeukocidinsMiceStaphylococcal Skin InfectionsBacterial ToxinsExotoxinsLeukocidinsPanton-Valentine leukocidin

Identifiers

PMID26618545
PMCPMC4664407
OpenAlexW2188083138

What OpenQuestion holds

Textmetadata
LicenceCC0
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.