Document Detail

Lethal Factor, but Not Edema Factor, Is Required to Cause Fatal Anthrax in Cynomolgus Macaques after Pulmonary Spore Challenge.
MedLine Citation:
PMID:  25285720     Owner:  NLM     Status:  Publisher    
Inhalational anthrax is caused by inhalation of Bacillus anthracis spores. The ability of B. anthracis to cause anthrax is attributed to the plasmid-encoded A/B-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. To better understand the contribution of these toxins to the disease pathophysiology in vivo, we used B. anthracis Ames strain and isogenic toxin deletion mutants derived from the Ames strain to examine the role of lethal toxin and edema toxin after pulmonary spore challenge of cynomolgus macaques. Lethal toxin, but not edema toxin, was required to induce sustained bacteremia and death after pulmonary challenge with spores delivered via bronchoscopy. After intravenous challenge with bacilli to model the systemic phase of infection, lethal toxin contributed to bacterial proliferation and subsequent host death to a greater extent than edema toxin. Deletion of protective antigen resulted in greater loss of virulence after intravenous challenge with bacilli than deletion of lethal toxin or edema toxin alone. These findings are consistent with the ability of anti-protective antigen antibodies to prevent anthrax and suggest that lethal factor is the dominant toxin that contributes to the escape of significant numbers of bacilli from the thoracic cavity to cause anthrax after inhalation challenge with spores.
Julie A Hutt; Julie A Lovchik; Melissa Drysdale; Robert L Sherwood; Trevor Brasel; Mary F Lipscomb; C Rick Lyons
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-3
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-6     Completed Date:  -     Revised Date:  2014-10-7    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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