PUBLICATION

A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens

Authors
Prajsnar, T.K., Cunliffe, V.T., Foster, S.J., and Renshaw, S.A.
ID
ZDB-PUB-080826-33
Date
2008
Source
Cellular Microbiology   10(11): 2312-2325 (Journal)
Registered Authors
Cunliffe, Vincent, Renshaw, Steve A.
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Disease Models, Animal*
  • Humans
  • Oligonucleotides, Antisense/genetics
  • Oligonucleotides, Antisense/metabolism
  • Phagocytes/immunology*
  • Phagocytosis/physiology
  • Recombinant Fusion Proteins
  • Staphylococcal Infections/immunology*
  • Staphylococcal Infections/mortality
  • Staphylococcus aureus/genetics
  • Staphylococcus aureus/immunology
  • Staphylococcus aureus/pathogenicity*
  • Survival Rate
  • Zebrafish/embryology
  • Zebrafish/immunology*
  • Zebrafish/microbiology*
PubMed
18715285 Full text @ Cell. Microbiol.
Abstract
With the emergence of multiply resistant Staphylococcus aureus, there is an urgent need to better understand the molecular determinants of S. aureus pathogenesis. A model of staphylococcal pathogenesis in zebrafish embryos has been established, in which host phagocytes are able to mount an effective immune response, preventing overwhelming infection from small inocula. Myeloid cell depletion, by pu.1 morpholino-modified antisense injection, removes this immune protection. Macrophages and neutrophils are both implicated in this immune response, phagocytosing circulating bacteria. In addition, in vivo phagocyte/bacteria interactions can be visualized within transparent embryos. A preliminary screen for bacterial pathogenesis determinants has shown that strains bearing mutations in perR, pheP and saeR are attenuated. perR and pheP mutants are deficient in growth in vivo, and their virulence is not fully restored by myeloid cell depletion. On the other hand, saeR mutants are able to grow in vivo, and are completely restored to virulence by myeloid cell depletion. Thus specific pathogen gene function can be matched with particular facets of host response. Zebrafish are a new addition to the tools available for the study of S. aureus pathogenesis, and may provide insights into the interactions of bacterial and host genomes in determining the outcome of infection.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping