Anthrax toxin entry into host cells

Anthrax toxin entry into host cells is a process mediated by the high-affinity binding of protective antigen (PA), a subunit of the anthrax toxin, to specific cell-surface receptors, primarily CMG2 (ANTXR2) and TEM8 (ANTXR1)[1][2][3][5][7]. Upon binding, PA is proteolytically cleaved and oligomerizes, recruiting the enzymatic toxin subunits (LF and EF). This receptor-toxin complex is subsequently internalized via clathrin-mediated endocytosis. Acidification in the endosome triggers formation of a translocon pore by PA, allowing LF and EF to translocate into the cytoplasm, where they disrupt cell signaling and contribute to disease pathology. While other proteins such as β1-integrin and LRP6 may act as accessory factors, CMG2 and TEM8 are considered the canonical entry receptors. Therapies targeting the interaction between PA and its receptors are in development, but the physiological role of the receptors themselves is still incompletely characterized, raising safety and efficacy concerns for drug targeting.

Other names

Capillary morphogenesis gene 2 (CMG2, ANTXR2)Tumor endothelial marker 8 (TEM8, ANTXR1)Anthrax toxin receptor 2 (ANTXR2)Anthrax toxin receptor 1 (ANTXR1)

Therapeutic agents: Block receptor interaction with protective antigen (PA), preventing toxin internalization. Antibodies: Neutralize PA or block receptor binding.