Figure 1.

Intoxication pathways of hemolysin B (Hbl), non-hemolytic enterotoxin (Nhe), cytotoxin K (Cyt K), CPB, CPE and staphylococcal enterotoxins (SEs). (A) Proposed mechanism of B. cereus enterotoxins, Hbl, Nhe and Cyt K. Hbl, Nhe and CytK begin their cytotoxic pathway by forming cell membrane pores that lead to the influx of Ca²⁺ and Na⁺ and the efflux of K⁺ and ATP and thereby to the loss of electrolytes and cell death. (B) Intracellular action of C. perfringens beta-toxin (CPB). Once CPB binds to ATP-gated P2X7 receptor, ATP is released from target cells to ATP-release channel pannexin 1. Induced by ATP release, CPB is oligomerized and a pore is formed. Pore formation leads to increased influx of Ca²⁺ that triggers calpain activation and necroptosis. Furthermore, pore formation also results in loss of intracytoplasmic K⁺ (iK⁺) that is associated with the activation of MAPK and JNK that are responsible for host cell survival and defense pathways. (C) Intracellular action of C. perfringens enterotoxin (CPE). CPE binds to its cellular receptor, claudin, and forms a small complex. Later on, six small CPE complexes oligomerized forming a prepore on the plasma membrane called CH-1. Assembly of β-hairpin loops into a β-barrel structure allows a cation-permeating pore insertion in the plasma membrane. The influx of Ca²⁺ stimulates calpain activity and thus the activation of caspase-3 and apoptosis. (D) SE-associated gastrointestinal (GI) inflammatory injury. Once they get endocytosed, SEs bind to MHC II class molecules and subsequently attract CD4⁺ T cells. Afterwards, an excessive production of pro inflammatory chemokines and cytokines is induced. Created with biorender.com (accessed on 28 May 2020).