Investigation of a Bacterial Pore-forming Chimera Toxin for Application as a Novel Drug-delivery System Tool

Background/Aim: Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins from Gram-positive bacteria. The aim of this study was to investigate the potential of a CDC, intermedilysin, as a drug-delivery system (DDS) for clinical application. Materials and Methods: Intermedilysin was modified by the addition of a disulfide bridge to regulate pore formation, by swapping domain 4 to provide cholesterol-binding capacity, and by the introduction of a targeting domain. The resultant chimera protein, His-LTBP-CDC(ss)IP, was investigated for its use as a DDS tool in vitro. Results: His-LTBP-CDC(ss)IP exhibited a regulated pore-forming capacity under reducing conditions. This chimera protein was able to deliver a drug-carrier liposome specifically to the target cell, to be endocytosed into the cell with subsequent release of the components into the cytoplasm. Conclusion: A chimera protein derived from the bacterial pore-forming toxin intermedilysin (His-LTBP-CDC(ss)IP) forms the basis for a novel DDS tool.