Transcription of the major Bacillus anthracis virulence genes is triggered by 
CO2, a signal mimicking the host environment. A 182-kb plasmid, pXO1, carries 
the anthrax toxin genes and the genes responsible for their regulation of 
transcription, namely atxA and, pagR, the second gene of the pag operon. AtxA 
has major effects on the physiology of B. anthracis. It coordinates the 
transcription activation of the toxin genes with that of the capsule 
biosynthetic enzyme operon, located on the second virulence plasmid, pXO2. In 
rich medium, B. anthracis synthesises alternatively two S-layer proteins (Sap 
and EA1). An exponential phase "Sap-layer" is subsequently replaced by a 
stationary phase "EA1-layer". S-layer gene transcription is controlled by 
alternative sigma factors and by Sap acting as a transcriptional repressor of 
eag. Furthermore, in vitro in presence of CO2 and in vivo, AtxA is part of the 
sap and eag regulatory network. Only eag is significantly expressed in these 
conditions and this is due to AtxA activating eag and repressing sap 
transcription. PagR, and not AtxA itself, is the direct effector of this 
regulation by binding to sap and eag promoter regions. Therefore, PagR mediates 
the effect of AtxA on eag and sap and is the most downstream element of a 
signalling cascade initiated by AtxA. Taken together, these results indicate 
that the B. anthracis transcriptional regulator AtxA is controlling the 
synthesis of the three toxin components and of the surface elements (capsule and 
S-layer). Thus, AtxA is a master regulator that coordinates the response to host 
signals by orchestrating positive and negative controls over genes located on 
all genetic elements.