Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice

Aaron M. Firoved, Georgina F. Miller, Mahtab Moayeri, Rahul Kakkar, Yuequan Shen, Jason F. Wiggins, Elizabeth M. McNally, Wei Jen Tang, Stephen H. Leppla*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death to BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, lethal toxin. Observations of gross pathology showed intestinal intralumenal fluid accumulation followed by focal hemorrhaging of the ileum and adrenal glands. Histopathological analyses of timed tissue harvests revealed lesions in several tissues including adrenal glands, lymphoid organs, bone, bone marrow, gastrointestinal mucosa, heart, and kidneys. Concomitant blood chemistry analyses supported the induction of tissue damage. Several cytokines increased after ET administration, including granulocyte colony-stimulating factor, eotaxin, keratinocyte-derived cytokine, MCP-1/JE, interleukin-6, interleukin-10, and interleukin-10. Physiological measurements also revealed a concurrent hypotension and bradycardia. These studies detail the extensive pathological lesions caused by ET and suggest that it causes death due to multiorgan failure.

Original languageEnglish (US)
Pages (from-to)1309-1320
Number of pages12
JournalAmerican Journal of Pathology
Volume167
Issue number5
DOIs
StatePublished - Nov 2005

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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