Fusion protein of Delta 27LFn and EFn has the potential as a novel anthrax toxin inhibitor

FEBS Lett. 2009 Apr 17;583(8):1257-60. doi: 10.1016/j.febslet.2009.03.053. Epub 2009 Mar 28.

Abstract

PA-binding domain of LF (LFn) or PA-binding domain of EF (EFn) is the anthrax protective antigen (PA) binding domain of anthrax lethal factor (LF) or edema factor (EF). Here we show the development of a novel anthrax toxin inhibitor, fusion protein of N-terminal 27 amino acids deletion of LFn (Delta27LFn) and EFn. In a cell model of intoxication, fusion protein of Delta27LFn and EFn (Delta27LFn-EFn) was a 62-fold more potent toxin inhibitor than LFn or EFn, and this increased activity corresponded to a 39-fold higher PA-binding affinity by Biacore analysis. More importantly, Delta27LFn-EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Delta27LFn-EFn has the potential as a candidate therapeutic agent against anthrax.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / toxicity
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / toxicity
  • Base Sequence
  • DNA Primers
  • Electrophoresis, Polyacrylamide Gel
  • Male
  • Rats
  • Rats, Inbred F344
  • Recombinant Fusion Proteins / pharmacology*

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • DNA Primers
  • Recombinant Fusion Proteins
  • anthrax toxin