title: The roles of AtxA orthologs in virulence of anthrax-like Bacillus cereus G9241.
abstract: AtxA is a critical transcriptional regulator of plasmid-encoded virulence genes in Bacillus anthracis. Bacillus cereus G9241, which caused an anthrax-like infection, has two virulence plasmids, pBCXO1 and pBC210, that each harbor toxin genes and a capsule locus. G9241 also produces two orthologs of AtxA: AtxA1, encoded on pBCXO1, and AtxA2, encoded on pBC210. The amino acid sequence of AtxA1 is identical to that of AtxA from B. anthracis, while the sequences of AtxA1 and AtxA2 are 79% identical and 91% similar to one another. We found by qRT-PCR that AtxA1 and AtxA2 function as positive regulators of toxin (AtxA1) and capsule operon (both) transcription in G9241 and that a ΔatxA1 mutant produced lower levels of the anthrax toxins and no hyaluronic acid capsule. Deletion of atxA1 or atxA2 decreased the virulence of spores administered intranasally or subcutaneously to C57BL/6 mice but not to A/J mice, and deletion of both genes rendered spores avirulent in A/J mice. In addition, unlike AtxA1, AtxA2 did not form stable homomultimers in vitro, although AtxA1 and AtxA2 formed heterodimers. Our data show that AtxA1 is the primary regulator of G9241 virulence factor expression and that AtxA1 and AtxA2 are both required for full virulence.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Scarff
authors.affiliation: Department of Microbiology and Molecular Genetics, The University of Texas Health Sciences Center at Houston, Houston, TX, USA.
authors.forename: Malik J
authors.initials: MJ
authors.lastname: Raynor
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Yuliya I
authors.initials: YI
authors.lastname: Seldina
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Ventura
authors.affiliation: Department of Microbiology and Molecular Genetics, The University of Texas Health Sciences Center at Houston, Houston, TX, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koehler
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Alison D
authors.initials: AD
authors.lastname: O'Brien
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism; D001408:Bacillus anthracis / Q000235:genetics / Q000378:metabolism; D001409:Bacillus cereus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D016667:Bacterial Capsules / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism; D005260:Female; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D009876:Operon / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014774:Virulence / Q000235:genetics*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: C082932:ATXA protein, Bacillus anthracis; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015534:Trans-Activators; D037521:Virulence Factors; C030325:anthrax toxin