Bacillus anthracis protective antigen (PA) (PA)

Bacillus anthracis protective antigen (PA) is a critical 83 kDa protein component of the tripartite toxin produced by the bacterium Bacillus anthracis, the causative agent of anthrax [1, 10]. PA serves as the receptor-binding and translocation subunit (B-component) that facilitates the entry of the enzymatic A-components, lethal factor (LF) and edema factor (EF), into host cells [4, 11]. Upon binding to host cell receptors such as capillary morphogenesis protein 2 (CMG2) or tumor endothelial marker 8 (TEM8), PA is cleaved by host proteases into a 63 kDa fragment (PA63) that oligomerizes into a heptameric or octameric prepore [2, 8]. This prepore then binds LF and EF, undergoes endocytosis, and forms a membrane-spanning channel in the acidic environment of the endosome to translocate the toxins into the cytosol [4, 8]. Because PA is essential for the assembly and delivery of both lethal and edema toxins, it is the primary target for anthrax vaccines and therapeutic monoclonal antibodies [1, 14]. Drugs like raxibacumab and obiltoxaximab work by binding to PA and preventing its interaction with host receptors, thereby neutralizing the toxin's effects and preventing the progression of the disease [2, 14]. Additionally, PA is used as a diagnostic biomarker, as its presence in serum correlates with the level of bacteremia and disease severity [5]. The protein's structure consists of four domains, with domain 4 being primarily responsible for receptor binding and domain 2 involved in pore formation [1, 10].

Other names

PA83PA63pagAProtective antigenpag

Neutralization of the protective antigen to prevent its binding to host cell receptors (CMG2 and TEM8), thereby blocking the entry of lethal factor and edema factor into the cytosol [4, 14].