Anthrax toxin and genetic aspects regulating its expression

Anthrax toxin is a unique, tripartite bacterial toxin, capable of causing edema and lethality through binary combinations of protective antigen (PA) with either edema factor (EF) or lethal factor (LF). The toxin-encoding genes (pagA, lef, cya) are maintained on a ~44 kb pathogenicity island (PAI), found on the large plasmid, pXO1. The toxin encoding genes are subject to inducible expression in response to CO2 and temperature through regulation by AtxA, which is also encoded by the pXO1 PAI. AtxA activity is not limited to toxin expression, as it influences the expression of chromosomal genes and genes involved in capsule synthesis found on a second large plasmid, pXO2. Thus, AtxA appears to be a major global regulator of inducible gene expression in B. anthracis. In response to AtxA induction, pagA is expressed as the first gene of the bicistronic operon, which also encodes pagR. PagR functions as an autogenous negative regulator of pagA expression and also modulates expression of two proteins involved in S-layer synthesis, thereby linking cell wall synthesis with toxin production. Therefore, expression of PA is subject to both positive and negative regulation. The review chapter presented here highlights the activity of anthrax toxin and the intertwining regulatory network that leads to AtxA-regulated, growth-dependent expression of PA, LF, and EF.