Fusion protein of Δ27LFn and EFn has the potential as a novel anthrax toxin inhibitor

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 (Δ27LFn) and EFn. In a cell model of intoxication, fusion protein of Δ27LFn and EFn (Δ27LFn–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, Δ27LFn–EFn could protect the highly susceptible Fischer 344 rats from anthrax lethal toxin challenge. This work suggested that Δ27LFn–EFn has the potential as a candidate therapeutic agent against anthrax.

Structured summary

MINT-7014735, MINT-7014747, MINT-7014761: PA63 (uniprotkb:P13423) and LF (uniprotkb:P15917) bind (MI:0407) by surface plasmon resonance (MI:0107)

Abbreviations: PA, protective antigen, LF, lethal factor, EF, edema factor, LFn, PA-binding domain of LF, EFn, PA-binding domain of EF, Δ27LFn, N-terminal 27 amino acids deletion of LFn, Δ27LFn–EFn, fusion protein of Δ27LFn and EFn

Keywords: Anthrax toxin, PA-binding domain of LF, PA-binding domain of EF, Toxin inhibitor, Fusion protein