HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pseudomonas aeruginosa cytotoxin ExoU is injected into phagocytic cells during acute pneumonia.

Abstract
ExoU, a cytotoxin translocated into host cells via the type III secretion system of Pseudomonas aeruginosa, is associated with increased mortality and disease severity. We previously showed that impairment of recruited phagocytic cells allowed survival of ExoU-secreting P. aeruginosa in the lung. Here we analyzed types of cells injected with ExoU in vivo using translational fusions of ExoU with a beta-lactamase reporter (ExoU-Bla). Cells injected with ExoU-Bla were detectable in vitro but not in vivo, presumably due to the rapid cytotoxicity induced by the toxin. Therefore, we used a noncytotoxic ExoU variant, designated ExoU(S142A)-Bla, to analyze injection in vivo. We determined that phagocytic cells in the lung were frequently injected with ExoU(S142A). Early during infection, resident macrophages constituted the majority of cells into which ExoU was injected, but neutrophils and monocytes became the predominant types of cells into which ExoU was injected upon recruitment into the lung. We observed a modest preference for injection into neutrophils over injection into other cell types, but in general the repertoire of injected immune cells reflected the relative abundance of these cells in the lung. Our results indicate that phagocytic cells in the lung are injected with ExoU and support the hypothesis that ExoU-mediated impairment of phagocytes has a role in the pathogenesis of pneumonia caused by P. aeruginosa.
AuthorsMaureen H Diaz, Alan R Hauser
JournalInfection and immunity (Infect Immun) Vol. 78 Issue 4 Pg. 1447-56 (Apr 2010) ISSN: 1098-5522 [Electronic] United States
PMID20100855 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Bacterial Proteins
  • Recombinant Fusion Proteins
  • pseudomonas exoprotein A protein, Pseudomonas aeruginosa
  • beta-Lactamases
Topics
  • Animals
  • Bacterial Proteins (metabolism)
  • Female
  • Genes, Reporter
  • Lung (immunology, pathology)
  • Macrophages (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Monocytes (immunology)
  • Neutrophils (immunology)
  • Pneumonia, Bacterial (immunology, microbiology)
  • Pseudomonas aeruginosa (immunology, pathogenicity)
  • Recombinant Fusion Proteins (genetics, metabolism)
  • beta-Lactamases (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: