Abstract
The development of cardiovascular dysfunction and shock in patients with invasive Bacillus anthracis infection has a particularly poor prognosis. Growing evidence indicates that several bacterial components likely play important pathogenic roles in this injury. As with other pathogenic Gram-positive bacteria, the B. anthracis cell wall and its peptidoglycan constituent produce a robust inflammatory response with its attendant tissue injury, disseminated intravascular coagulation and shock. However, B. anthracis also produces lethal and edema toxins that both contribute to shock. Growing evidence suggests that lethal toxin, a metalloprotease, can interfere with endothelial barrier function as well as produce myocardial dysfunction. Edema toxin has potent adenyl cyclase activity and may alter endothelial function, as well as produce direct arterial and venous relaxation. Furthermore, both toxins can weaken host defense and promote infection. Finally, B. anthracis produces non-toxin metalloproteases which new studies show can contribute to tissue injury, coagulopathy and shock. In the future, an understanding of the individual pathogenic effects of these different components and their interactions will be important for improving the management of B. anthracis infection and shock.
Highlights
Recent outbreaks of Bacillus anthracis infection in the United States (US) and Europe have underscored the importance of this bacterium in the developed world [1,2,3,4]
An understanding of the individual pathogenic effects of these different components and their interactions will be important for improving the management of B. anthracis infection and shock
Lethal toxin (LT) and Edema toxin (ET) have long been a focus in this area of research, newer data have begun to emphasize the role of these non-toxin components
Summary
Recent outbreaks of Bacillus anthracis infection in the United States (US) and Europe have underscored the importance of this bacterium in the developed world [1,2,3,4]. These changes occurred in patterns similar to those in patients with B. anthracis infection and shock; and were greater in non-survivors than survivors Hemodynamic effects such as these frequently reflect peripheral vascular dysfunction related either to endothelial barrier dysfunction with extravasation of fluid or direct dilation of arterial resistance or venous capacitance vessels. Pretreatment of rats with sub-lethal LT doses inhibited inflammatory mediator release stimulated by lipopolysaccharide (LPS) or E. coli challenges [14] These inhibitory effects of LT on immune responses have been proposed as a basis for the high bacterial loads noted in patients dying with B. anthracis infection [13,19,21,22]. What the relative roles are of LF and these other metalloproteases during shock in patients with B. anthracis infections require study
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