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

J Infect Dis. 2013 Sep;208(6):978-89. doi: 10.1093/infdis/jit247. Epub 2013 Jun 3.

Abstract

Background: 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.

Keywords: Bacillus anthracis; anthrax infection; coagulopathy; disseminated intravascular coagulation; edema toxin; lethal toxin; peptidoglycan; sepsis; thrombocytopenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthrax / blood*
  • Anthrax / pathology
  • Antigens, Bacterial / toxicity*
  • Antithrombin III
  • Bacillus anthracis
  • Bacterial Toxins / toxicity*
  • Blood Coagulation
  • Cell Wall / chemistry*
  • Disseminated Intravascular Coagulation / blood*
  • Disseminated Intravascular Coagulation / microbiology
  • Fibrinogen / metabolism
  • Nitric Oxide / blood
  • Partial Thromboplastin Time
  • Peptide Hydrolases / blood
  • Peptidoglycan / toxicity*
  • Plasminogen Inactivators / blood
  • Protein C / metabolism
  • Prothrombin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Thromboplastin / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • Peptidoglycan
  • Plasminogen Inactivators
  • Protein C
  • anthrax toxin
  • antithrombin III-protease complex
  • Nitric Oxide
  • Antithrombin III
  • Prothrombin
  • Fibrinogen
  • Thromboplastin
  • Peptide Hydrolases