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Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo.

Abstract
Anthrax toxin, a major virulence factor of Bacillus anthracis, gains entry into target cells by binding to either of 2 von Willebrand factor A domain-containing proteins, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2). The wide tissue expression of TEM8 and CMG2 suggest that both receptors could play a role in anthrax pathogenesis. To explore the roles of TEM8 and CMG2 in normal physiology, as well as in anthrax pathogenesis, we generated TEM8- and CMG2-null mice and TEM8/CMG2 double-null mice by deleting TEM8 and CMG2 transmembrane domains. TEM8 and CMG2 were found to be dispensable for mouse development and life, but both are essential in female reproduction in mice. We found that the lethality of anthrax toxin for mice is mostly mediated by CMG2 and that TEM8 plays only a minor role. This is likely because anthrax toxin has approximately 11-fold higher affinity for CMG2 than for TEM8. Finally, the CMG2-null mice are also shown to be highly resistant to B. anthracis spore infection, attesting to the importance of both anthrax toxin and CMG2 in anthrax infections.
AuthorsShihui Liu, Devorah Crown, Sharmina Miller-Randolph, Mahtab Moayeri, Hailun Wang, Haijing Hu, Thomas Morley, Stephen H Leppla
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 30 Pg. 12424-9 (Jul 28 2009) ISSN: 1091-6490 [Electronic] United States
PMID19617532 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
Chemical References
  • Antigens, Bacterial
  • Antxr1 protein, mouse
  • Antxr2 protein, mouse
  • Bacterial Toxins
  • Biomarkers, Tumor
  • Membrane Proteins
  • Receptors, Peptide
  • anthrax toxin
Topics
  • Animals
  • Anthrax (metabolism, microbiology)
  • Antigens, Bacterial (metabolism)
  • Bacillus anthracis (metabolism, physiology)
  • Bacterial Toxins (metabolism)
  • Binding Sites
  • Biomarkers, Tumor
  • Blotting, Western
  • Cells, Cultured
  • Female
  • Fibroblasts (cytology, metabolism)
  • Gene Expression
  • Genes, Essential (genetics)
  • Host-Pathogen Interactions
  • Male
  • Membrane Proteins (genetics, metabolism)
  • Mice
  • Mice, Knockout
  • Receptors, Peptide (genetics, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spores, Bacterial (growth & development)

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