Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model

Xizhong Cui, Yan Li, Xuemei Li, Michael W. Laird, Mani Subramanian, Mahtab Moayeri, Stephen H. Leppla, Yvonne Fitz, Junwu Su, Kevin Sherer, Peter Q. Eichacker

Research output: Contribution to journalArticle

Abstract

Introduction. To better define the contribution of edema toxins (ETx) and lethal toxins (LeTx) to shock with Bacillus anthracis, recombinant preparations of each were investigated alone or together in rats. Methods and results. Lethal dose ranges (0%-100% lethality) of ETx (200-800 μg/kg as a 24-h infusion) were higher than those of LeTx (12.5-200 μg/kg) (P < .0001). However, compared with LeTx, similarly lethal ETx doses produced earlier and greater reductions in mean blood pressure (MBP) and increased, rather than decreased, heart rate (HR) (P < .05 for all). Combining either similar weight or lethal doses of ETx and LeTx increased the hazard ratio for death (log ± standard error) similar to the sum calculated with the toxin's effects alone (2.6 ± 1.1 observed vs. 2.9 ± 1.0 calculated for similar weight and 3.1 ± 1.0 vs. 3.9 ± 1.5 for similar lethal doses; P = .5 for both). Early (≤10 h) and late during infusion, ETx and LeTx together also altered MBP and HR in patterns consistent with the sum of their individual effects. Conclusions. ETx was ∼10 times less lethal than LeTx but produced greater hypotension and added to the latter's harmful effects. These findings suggest that it may be appropriate for antitoxin therapies for B. anthracis to target both ETx and LeTx.

Original languageEnglish (US)
Pages (from-to)572-580
Number of pages9
JournalJournal of Infectious Diseases
Volume195
Issue number4
DOIs
StatePublished - Feb 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Cui, X., Li, Y., Li, X., Laird, M. W., Subramanian, M., Moayeri, M., Leppla, S. H., Fitz, Y., Su, J., Sherer, K., & Eichacker, P. Q. (2007). Bacillus anthracis edema and lethal toxin have different hemodynamic effects but function together to worsen shock and outcome in a rat model. Journal of Infectious Diseases, 195(4), 572-580. https://doi.org/10.1086/510856