“…Most of these toxins are composed of four structural modules: an N-terminal glucosyltransferase domain (GTD), followed by a cysteine protease domain (CPD), a delivery and receptor-binding domain (DRBD), and a large C-terminal combined repetitive oligopeptides domain (CROPs) ( Aktories et al, 2017 ; Orrell & Melnyk, 2021 ) ( Fig 1A ). The cellular uptake of TcdA and TcdB are mediated by receptor-mediated endocytosis ( Papatheodorou et al, 2010 ; Tao et al, 2016 , 2019 ; Aktories et al, 2017 ; Chen et al, 2018 , 2021 ). Triggered by acidification in the endosomes, the hydrophobic pore-forming region of the toxin undergoes membrane insertion and facilitates the translocation of the GTD and the CPD into the cytosol ( Qa’Dan et al, 2000 ; Barth et al, 2001 ; Genisyuerek et al, 2011 ; Zhang et al, 2014 ).…”