Evidence map›Paper›PMID 21525981›Full record

ArticlePloS one2011

Global changes in Staphylococcus aureus gene expression in human blood.

Natalia Malachowa, Adeline R Whitney, Scott D Kobayashi, Daniel E Sturdevant, Adam D Kennedy, Kevin R Braughton, Duncan W Shabb, Binh An Diep, Henry F Chambers, Michael Otto and 1 more

Abstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
156citing papers in PubMed, 1 pooled it
–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

156 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Host-Bacterium Interaction Mechanisms inInternational journal of molecular sciences · 2023
    Pooled it
  2. Infection and immunity · 2026
    Article
  3. Article
  4. Host-driven remodelling of theMicrobiology (Reading, England) · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Infection and immunity · 2025
    Review
  9. Article
  10. Review
  11. Linking Virulence and Iron Limitation Response inJournal of proteome research · 2025
    Article
  12. Metabolites · 2025
    Review
  13. Article
  14. Integrated genomic and proteomic analysis of the mouse-adaptedCurrent research in microbial sciences · 2025
    Article
  15. Forssman and the staphylococcal hemolysins.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review

96 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

11 authors.

Natalia MalachowaLaboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
Adeline R Whitney
Scott D Kobayashi
Daniel E Sturdevant
Adam D Kennedy
Kevin R Braughton
Duncan W Shabb
Binh An Diep
Henry F Chambers
Michael Otto
Frank R DeLeo

Funding

Staphylococcal pathogenesisZIAAI000904 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI OTTO, MICHAEL · 2009 to 2025
$22.6M
Mechanisms of Staphylococcus aureus virulenceZIAAI001079 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI DELEO, FRANK · 2009 to 2025
$11.8M
Mechanisms of PVL-induced Acute Lung InjuryR01AI087674 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DIEP, BINH AN · 2010 to 2014
$2.1M
Genetic Basis of Virulence of Community MRSA Clone USA300R01AI070289 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HENRY CHAMBERS, HENRY F · 2008 to 2010
$1.2M
Intramural NIH HHSNIAID NIH HHS R01 AI070289NIAID NIH HHS R01 AI087674
6 · The paper itself

Abstract

Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote survival in human blood and ultimately facilitate metastases is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Compared to culture supernatants from a wild-type USA300 strain (LAC), those derived from an isogenic hlgABC-deletion strain (LACΔhlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Moreover, LACΔhlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LACΔhlgABC strains caused virtually identical abscesses in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed functional redundancy among two-component leukotoxins in vitro. These findings, along with a requirement of specific growth conditions for leukotoxin expression, may explain the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence.

Indexed as

Gene Expression Regulation, BacterialAnimalsBacterial ProteinsBacterial ToxinsCell Membrane PermeabilityDisease Models, AnimalExotoxinsGene DeletionGene Expression ProfilingHemolysin ProteinsHumansMiceMicrobial ViabilityNeutrophilsPorosityRNA, MessengerBacterial ProteinsBacterial ToxinsExotoxinsgamma-hemolysin, Staphylococcus aureusHemolysin ProteinsleukotoxinRNA, Messenger

Identifiers

PMID21525981
PMCPMC3078114

What OpenQuestion holds

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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.