title: Toxicity of anthrax toxin is influenced by receptor expression.
abstract: Anthrax toxin protective antigen (PA) binds to its cellular receptor, and seven subunits self-associate to form a heptameric ring that mediates the cytoplasmic entry of lethal factor or edema factor. The influence of receptor type on susceptibility to anthrax toxin components was examined using Chinese hamster ovary (CHO) cells expressing the human form of one of two PA receptors: TEM8 or CMG2. Unexpectedly, PA alone, previously believed to only mediate entry of lethal factor or edema factor, was found to be toxic to CHO-TEM8 cells; cells treated with PA alone displayed reduced cell growth and decreased metabolic activity. PA-treated cells swelled and became permeable to membrane-excluded dye, suggesting that PA formed cell surface pores on CHO-TEM8 cells. While CHO-CMG2 cells were not killed by wild-type PA, they were susceptible to the PA variant, F427A. Receptor expression also conferred differences in susceptibility to edema factor.
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Taft
authors.forename: Alison A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018000:Receptors, Peptide / Q000096:biosynthesis*
chemical_list: C473287:ANTXR1 protein, human; C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors