Bacillus anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model

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DOIResolve DOI: http://doi.org/10.1093/infdis/jit247
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TypeArticle
Journal titleJournal of Infectious Diseases
ISSN0022-1899
Volume208
Issue6
Pages978989; # of pages: 12
Subjectanthrax infection; sepsis; coagulopathy; thrombocytopenia; Bacillus anthracis; disseminated intravascular coagulation; peptidoglycan; lethal toxin; edema toxin
AbstractBackground. Disseminated intravascular coagulation (DIC) appears to be important in the pathogenesis of Bacillus anthracis infection, but its causes are unclear. Although lethal toxin (LT) and edema toxin (ET) could contribute, B. anthracis cell wall peptidoglycan (PGN), not the toxins, stimulates inflammatory responses associated with DIC.Methods and Results. To better understand the pathogenesis of DIC during anthrax, we compared the effects of 24-hour infusions of PGN, LT, ET, or diluent (control) on coagulation measures 6, 24, or 48 hours after infusion initiation in 135 rats. No control recipient died. Lethality rates (approximately 30%) did not differ among PGN, LT, and ET recipients (P =. 78). Thirty-three of 35 deaths (94%) occurred between 6 and 24 hours after the start of challenge. Among challenge components, PGN most consistently altered coagulation measures. Compared with control at 6 hours, PGN decreased platelet and fibrinogen levels and increased prothrombin and activated partial thromboplastin times and tissue factor, tissue factor pathway inhibitor, protein C, plasminogen activator inhibitor (PAI), and thrombin-antithrombin complex levels, whereas LT and ET only decreased the fibrinogen level or increased the PAI level (P ≤. 05). Nearly all effects associated with PGN infusion significantly differed from changes associated with toxin infusion (P ≤. 05 for all comparisons except for PAI level).Conclusion. DIC during B. anthracis infection may be related more to components such as PGN than to LT or ET. © 2013 The Author.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number21270479
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Record identifiere9593893-0ea4-491e-90a5-60fbd2839c4f
Record created2014-02-13
Record modified2016-05-09
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