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Anthrax biosensor, protective antigen ion channel asymmetric blockade

  1. Author:
    Halverson, K. M.
    Panchal, R. G.
    Nguyen, T. L.
    Gussio, R.
    Little, S. F.
    Misakian, M.
    Bavari, S.
    Kasianowicz, J. J.
  2. Author Address

    Natl Inst Stand & Technol, Adv Chem Sci Lab, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Elect & Elect Engn Lab, Semicond Engn Div, Gaithersburg, MD 20899 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Target Struct Based Drug Discovery Grp, Sci Applicat Int Corp, Frederick, MD 21702 USA Kasianowicz, JJ, Natl Inst Stand & Technol, Adv Chem Sci Lab, Bldg 225,Rm B326, Gaithersburg, MD 20899 USA
    1. Year: 2005
    2. Date: OCT 7
  1. Journal: Journal of Biological Chemistry
    1. 280
    2. 40
    3. Pages: 34056-34062
  2. Type of Article: Article
  1. Abstract:

    The significant threat posed by biological agents ( e. g. anthrax, tetanus, botulinum, and diphtheria toxins) (Inglesby, T. V., O'Toole, T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Friedlander, A. M., Gerberding, J., Hauer, J., Hughes, J., McDade, J., Osterholm, M. T., Parker, G., Perl, T. M., Russell, P. K., and Tonat, K. ( 2002) J. Am. Med. Assoc. 287, 2236 - 2252) requires innovative technologies and approaches to understand the mechanisms of toxin action and to develop better therapies. Anthrax toxins are formed from three proteins secreted by fully virulent Bacillus anthracis, protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). Here we present electrophysiological measurements demonstrating that full-length LF and EF convert the current-voltage relationship of the heptameric PA(63) ion channel from slightly nonlinear to highly rectifying and diode-like at pH 6.6. This effect provides a novel method for characterizing functional toxin interactions. The method confirms that a previously well characterized PA(63) monoclonal antibody, which neutralizes anthrax lethal toxin in animals in vivo and in vitro, prevents the binding of LF to the PA(63) pore. The technique can also detect the presence of anthrax lethal toxin complex from plasma of infected animals. The latter two results suggest the potential application of PA(63) nanopore-based biosensors in anthrax therapeutics and diagnostics

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External Sources

  1. WOS: 000232229700045

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