Anthrax Virulence - created from Mind Map

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Multicomponent anthrax toxin: consists of 3 distinct antigenic componenet

Edema Factor (EF)

Lethal Factor (LF)

Protective Antigen (PA)

mediates toxigenic stage

production mediated by temperature-sensitive plasmid, pXO1

each component of the toxin is a thermolabile protein

Apart from their antigenicity, each of the 3 factors exhibits no significant biological activity.

inherent adenylate cyclase and works additively with lethal factor

increases cAMP production

immunosuppressive effect

Necessary for edema producing activity of the toxin

immunosuppressive effect

damages endothelial cell function and causes cell apoptosis

dirupts downstream cell signalling

Essential for the lethal effect of anthrax toxin

Zn++ dependant protease that induces sytokine production in macrophages & lymphocytes

Crystal structure is a member of the mitogen-activated protein kinase (MAPKK) family of enzymes

Known to disrupt cellular signaling

binding domain that allows toxins to enter host cell

induces protective antitoxic antibodies

Anthrax toxin receptor

Binding domain of anthrax toxin which has 2 active domians: EF & LF

Human receptor for anthrax PA demonstrated to be a type I membrane protein that bind directly to PA

Combination of 2 or 3 of the toxin components yeild the following results in experimental animals

Experiments suggest anthrax toxin has the familiar A-B enzymatic binding structure of bacteriual exotoxins

PA+LF combine to produce lethal activity

EF+PA produce edema

EF+LF is inactive

PA+LF+ED produces edema & necrosis & is lethal

elevates cAMP to extraordinary levels in susceptiable cells.

Intracellular changes in cAMP affect changes in membrane permeability & may account for edema

In macrophages & neutrophils: additioanl effect is depletion of ATP reserves which are needed for the engulfment process.

1 effect of toxin is to impair activity of regional phagocytes duuring infectious process

Phagocytosis by opsonized or heat-killed B. antheacis cells is not inhibited by either EF or LF

increased levels of cAMP in neutrophils

Studies suggest that 2 active components increase host susceptibilty to infection

BUT a combination of EF+LF inhibits engulfment of bacteria & the oxidative burst in the pmns

Supressing neutrophil function & impairing host resistance

PA acting as the B fragment & either EF or LF acting as the active A fragment

Poly-D-Glutamyl Capsule

Capsule production depends on plasmid pXO2

single antigenic type capsule consisting of D-glutamate polypeptide

capsule itself is none toxic

Play most important during role establishment of infection

Transefered to nonencapsulated B. anthracis via transduction produces an encapsulated phenotype

detection of capsular material used to distinguish from closest relatives

Prevents phagocytosis when in vegetative form.

function to protect organism against complement & bactericidal components of serum & phagocytes

Protect against phagocytic engulfment& destruction

Mediates the invasive stage of the infection

less significant role in the terminal phase of disease, which are mediated by anthrax toxin

Host immune response

EF & LF inbihits CT4 T-cell proliferation, neutrophile phagocytosis, cytokine production, IL-2 production & causes macrophage lysis.

macrophages ingest spores & transport them to regional lymphnodes

Produced anti-protective antigen IgG to combat toxins by neutralizing lethal factor

PA-specific IgG memory B cells are prodcued in infected

Spores used macrophage tobypass immune system

Coordinates expression of virielnce factors in response to environmental signal

Toxin protiens & antiphagocytic capsule are produced in response to growth in increased atmospheric CO2

CO2 signal is thought to be of physiological significance for a pathogen which invades mammalian host tissue

Anthrax Virulence