Anthrax edema toxin impairs protein clearance in mice

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NIAID	INFECTDIS-12

Authors

• I Sastalla
• S Tang
• D Crown
• S Liu
• MA Eckhaus
• IK Hewlett
• SH Leppla
• M Moayeri

Abstract

Anthrax edema toxin (ET) of Bacillus anthracis raises intracellular concentrations of the secondary messenger cAMP in host cells. We report here that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer in vitro and in vivo through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and non-myeloid cells. Our data suggest that in vivo, ET alters circulatory protein pharmacokinetics as evidenced by impaired clearance of ovalbumin when co-injected with this toxin in mice. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. The effect of ET on protein clearance is a novel in vivo effect of this toxin.

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