title: Bacillus anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model.
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.
  
  
  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).
  
  
  CONCLUSIONS
  DIC during B. anthracis infection may be related more to components such as PGN than to LT or ET.
authors.affiliation: Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Joseph
authors.initials: J
authors.lastname: Shiloach
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Junfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Loc
authors.initials: L
authors.lastname: Trinh
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubler-Kielb
authors.forename: Evgeny
authors.initials: E
authors.lastname: Vinogradov
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.forename: Mariam
authors.initials: M
authors.lastname: Al-Hamad
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Fitz
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000881:Anthrax / Q000097:blood* / Q000473:pathology; D000942:Antigens, Bacterial / Q000633:toxicity*; D000990:Antithrombin III; D001408:Bacillus anthracis; D001427:Bacterial Toxins / Q000633:toxicity*; D001777:Blood Coagulation; D002473:Cell Wall / Q000737:chemistry*; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000382:microbiology; D005340:Fibrinogen / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000097:blood; D010457:Peptidoglycan / Q000633:toxicity*; D015849:Plasminogen Inactivators / Q000097:blood; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D010457:Peptidoglycan; D015849:Plasminogen Inactivators; D011486:Protein C; C030325:anthrax toxin; C046193:antithrombin III-protease complex; D009569:Nitric Oxide; D000990:Antithrombin III; D011516:Prothrombin; D005340:Fibrinogen; D013925:Thromboplastin; D010447:Peptide Hydrolases
keywords: Bacillus anthracis; anthrax infection; coagulopathy; disseminated intravascular coagulation; edema toxin; lethal toxin; peptidoglycan; sepsis; thrombocytopenia