Edema toxin

Produces lethal and edema toxins to kill the target host cell... 

Edema toxin does not produce major tissue damage. In fact, its major role is to impair phagocyte function (Leppla, 2000). This is consistent with other toxins which fimction to elevate cAMP concentrations. Edema toxin inhibits phagocytosis of spores by human PMNs (O Brien et al, 1985) similar to LF this is in contrast to spores which promote immune cell uptake (see Table 31.1). Increased intracellular cAMP induced by EF inhibits neutrophil chemotaxis, phagocytosis, superoxide production, and microbicidal activity (Crawford et al, 2006 Turk, 2007 O Brien et al, 1985 Friedman et al, 1987 O Dowd et al, 2004 Ahmed et al, 1995). EF has been shown to inhibit TNFa and increase IL-6 production (Hoover et al, 1994). Increased cAMP levels also block LPS-induced activation... 

Hoover, D.L., Friedlander, A.M., Rogers, L.C., Yoon, I.K., Warren, R.L., Cross, A.S. (1994). Anthrax edema toxin differentially regulates lipopolysaccharide-induced monocyte production of tumor necrosis factor a and interleukin-6 by increasing intracellular cyclic AMP. Infect. Immun. 62 4432-9. 

Toumier, J.N., Quesnel-Hellmann, A., Mathieu, J., Montecucco, C., Tang, W.J., Mock, M., Vidal, D.R., Goossens, P.L. (2005). Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J. Immunol. 174 4934-41. 

Anthrax toxin is composed of three proteins protective antigen (PA 83kDa), lethal factor (LF 90kDa), and edema factor (EF 89kDa). Individually, none of the three proteins are toxic but interact synergistically with at least one of the others. PA and LF (called LeTx) can cause lethal shock in experimental animals, and a mixture of PA and EF (edema toxin, EdTx) induces edema at the site of injection. Since two discrete units of the toxin are required for its action, the term binary toxin has been used to this and other bacterial toxins. Anthrax is unique from other binary toxins in that the binary moieties (EF and LF) interact only after being secreted from the bacteria. Further, EF and LF enter the cell via a single PA protein. Assembly of the three toxin proteins is initiated when PA binds to a proteinaceous cellular receptor and is activated by a member of the furin family of cellular proteases. The exact mechanisms of internalization of the toxin moieties are subject of scientific enquiry. Inside the cellular cytoplasm, EF (a calcium and calmodulin-dependent adenylate cyclase) causes a dramatic increase in intracellular cAMP concentrations and LF acts proteolytically to cleave certain MAPK kinases. 

Spores germinate to bacillary form, multiply in macrophages, release toxins causing edema, hemorrhage, and tissue necrosis tissue damage caused by release of toxins - protective antigen, lethal toxin, edema toxin [29]... 

B anthracis possesses three known virulence factors an antiphagocytic capsule and two protein exotoxins, called the lethal and the edema toxins. The role of the capsule in pathogenesis was demonstrated in the early 1900s, when anthrax strains lacking a capsule were shown to be avirulent.17 In more recent years, the genes encoding synthesis of the... 

The edema toxin, consisting of the same protective antigen together with a third protein, edema factor (MW 89,000), causes edema when injected into the skin of experimental animals.28,29 The edema... 

The situation in the infected animal may be somewhat different, since the toxin proteins may exist in the serum as a complex of protective antigen and lethal factor.39 It is possible that the proteolytic activation of protective antigen necessary to form lethal or edema toxin may occur in interstitial fluid or serum rather than on the cell surface. The lethal or the edema toxin may then bind to target cells and be internalized. 

Alteration in mental status occurring in patients with systanic sepsis always carries a serious prognosis. The mechanisms of impaired brain function are poorly understood and are probably multifactorial. Considerations include hypoxia, ischemia, mitochondrial dysfunction and anaerobic cerebral energy metabolism, blood-brain barrier dysfunction or impaired transporter function, cerebral edema, toxins like ammonia or endotoxins, and last but not least, clinical use of cerebral depressants and sedatives in severely ill patients. In patients with multi-organ failure, clearance of common short-acting sedatives can become prolonged, resulting in severe and protracted alteration of mentation. 

Edema Toxin (EdTx) and Lethal Toxin (LeTx) are two toxins with immunomodulatory activity that are produced by A anthracis, the cause of the disease anthrax. Both toxins are composed of a heptameric complex of protective antigen (PA) bound to either edema factor (EF) or lethal factor (LF). " The heptameric complex of PA is responsible for receptor binding and cellular entry, whereas toxicity is associated with both EF, a calmodulin-dependent adenylate cyclase that induces increases in cytosolic cAMP and LF, a metalloprotease that cleaves mitogen-activated protein kinase kinases (MAPKK). ... 

Duverger A, Jackson RJ, van Ginkel FW et al. Bacillus anthracis edema toxin acts as an adjuvant for mucosal immune responses to nasally administered vaecine antigens. J Immunol 2006 176(3) 1776-1783. 

Comer JE, Galindo CL, Zhang F et al. Murine macrophage transcriptional and functional responses to bacillus anthracis edema toxin. Microb Pathog 2006 41(2-3) 96-110. 

Tournier JN, Quesnel Hellmann A, Mathieu J et al. Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J Immunol 2005 174(8) 4934-4941. 

Fioved, A.M., Miller, G.R, Moayeri, M., et al., 2005. Bacillus antkmcis edema toxin causes extensive tissue lesions and rapid lethality in mice. Am. J. Pathol. 167, 1309-1320. 

Sweeney, D.A., Cui, X, Solomon, S.B., et al., 2010. Anthrax lethal and edema toxin produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines. J. Infect. Dis. 202, 188-196. 

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