Edema toxin is a key virulence determinant in
anthrax pathogenesis that causes augmentation of cAMP inside host cells. This
exotoxin has been implicated in facilitating bacterial invasion by impairing host defenses. Here, we report for the first time that
edema toxin plays an important role in suppression of platelet aggregation; an effect that could be of vital significance in
anthrax afflicted subjects. It was found that
edema toxin induces a dose dependent and time dependent increase in cAMP inside rabbit platelets. Elevation of cAMP led to suppression of platelet aggregation as demonstrated by in vitro aggregation assays. A 95% suppression of platelet aggregation in response to
thrombin and a complete suppression in response to
ADP, at toxin concentrations of 7 and 2.2 nM, respectively, were observed. Antibody neutralized wild type
edema factor and non-toxic mutants of this binary toxin failed to show any alteration in the normal aggregation pattern.
Edema toxin caused the activation of
cAMP dependent protein kinase A inside platelets, a phenomenon that could be speculated to initiate the cascade of events responsible for suppressing platelet aggregation. Furthermore, in vivo bleeding time registered a sharp increase in response to
edema toxin. These findings can explicate the systemic occurrence of
hemorrhage, which is a prominent symptom of
anthrax. This study exemplifies how Bacillus anthracis has evolved the ability to use host's physiological processes by mimicking the eukaryotic signal transduction machinery, thus inflicting
persistent infection.