AB-type toxins are causative agents of several serious diseases, including cholera, diphtheria, pertussis, and intestinal disease. Following receptor-mediated endocytosis, the toxin is transported retrogradely from the Golgi apparatus to the endoplasmic reticulum (ER), followed by enzymatically active A-subunit transport from the ER-associated degradation (ERAD) pathway into the cytosol, or the A-subunit directly translocates from endosomes in a pH-dependent manner into the cytosol. In the cytosol, the A-subunits of toxins investigated in this thesis, covalently transfer an ADP (adenosine diphosphate)-ribose moiety or UDP (uridine diphosphate)-glucose moiety to their specific intracellular targets, leading to cellular reactions and potentially life-threatening clinical symptoms. Both intracellular uptake pathways require at least partial unfolding of the A-subunit for membrane translocation, followed by refolding of the A-subunit in the cytosol to restore enzyme activity. The folding helper enzymes such as Hsp90, Hsp/c70, cyclophilins (Cyps), FK506‐binding proteins (FKBPs) and TRiC/CCT (TCP-1 ring complex/chaperonin containing TCP-1) have been shown to facilitate the transport of the A-subunit into the cytosol and/or assist their refolding and stabilization. Inhibition of these host cell factors by their specific pharmacological inhibitors radicicol (Rad), VER-155008 (VER), cyclosporine A (CsA), FK506 or heat shock factor 1 activator (HSF1A), respectively, protects cells from intoxication with AB-type toxins. In this thesis, the inhibitory effect of the licensed drug domperidone (DOM), a novel inhibitor of the ATPase activity of Hsp70, on AB-type toxins was tested. I demonstrated that DOM protects cells from intoxication with Clostridium (C.) botulinum C2 toxin (C2 toxin), Corynebacterium diphtheriae toxin (DT), Clostridioides (C.) difficile toxins A (TcdA) and B (TcdB) by monitoring toxin-induced specific cell rounding due to disruption of the actin cytoskeleton. DOM showed a comparable inhibitory effect to VER. To elucidate the underlying inhibition mechanism, I ruled out inhibition of DOM on the enzyme component of Clostridium botulinum C2 toxin (C2I) in vitro enzyme activity or binding of C2 toxin to the cell surface. In addition, I analyzed the membrane translocation of C2I directly across the cytoplasmic membrane into the cytosol in an isolated manner and demonstrated that DOM interferes with exactly this step of toxin uptake. Moreover, pre-incubation of HeLa cells with DOM or VER inhibited the glucosylation of intracellular Rac1 induced by TcdB, and the inhibitory effect of DOM was comparable to VER. These results indicate that Hsp70 also plays a role during the uptake of TcdB into the cell. DOM reduced the amount of ADP-ribosylated Gαi (α-subunit of the trimeric inhibitory guanosine triphosphate-binding-protein) by pertussis toxin (PT) without inhibiting the enzyme activity of PTS1 (enzyme subunit of PT) and binding of PT to cells. Less PTS1 was detected in the host cell cytosol in the presence of DOM by fluorescence microscopy, suggesting that DOM inhibits the intracellular uptake step of PT and therefore protects cells from intoxication with PT. In addition to DOM, I have also demonstrated the inhibitory effects of HSF1A and amiodarone (Ami) on PT in this thesis. HSF1A is a specific inhibitor of TRiC/CCT, which is involved in the refolding and restoration of the TcdB enzyme domain, while Ami, an approved antiarrhythmic drug, has been shown to protect cells from intoxication with anthrax toxin and DT by blocking endosomal acidification. Based on fluorescence microscopy and Western blot analysis, HSF1A and Ami were both shown to reduce the amount of PTS1 reaching the host cell cytosol and decrease the ADP-ribosylation of Gαi by PTS1 without affecting the binding of PT to cells, suggesting that TRiC/CCT may play a role in the intracellular uptake of PT, while Ami might affect the transport of PTS1 into the cytosol. Taken together, the potent inhibitory effect of DOM on the bacterial toxins shown in this thesis makes DOM a potential therapeutic approach against various diseases caused by bacterial AB-type toxins that require Hsp70 for cellular uptake. Therapies targeting TRiC/CCT as well as the application of Ami may be interesting strategies against PT-induced pertussis symptoms.