title: In vivo Bacillus anthracis gene expression requires PagR as an intermediate effector of the AtxA signalling cascade.
abstract: 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.
authors.affiliation: Unité Toxines et Pathogénie Bactérienne, CNRS URA 2172, Institut Pasteur, Paris, France.
authors.forename: Tâm
authors.initials: T
authors.lastname: Mignot
authors.forename: Evelyne
authors.initials: E
authors.lastname: Couture-Tosi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mesnage
authors.forename: Michèle
authors.initials: M
authors.lastname: Mock
authors.forename: Agnès
authors.initials: A
authors.lastname: Fouet
mesh_terms: D000881:Anthrax / Q000382:microbiology*; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006801:Humans; D012808:Sigma Factor / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D014774:Virulence
chemical_list: C082932:ATXA protein, Bacillus anthracis; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D012808:Sigma Factor; D015534:Trans-Activators; C030325:anthrax toxin