Investigation of a bacterial pore-forming chimera toxin for application as a novel drug-delivery system tool.
OBJECTIVE
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.


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.


CONCLUSIONS
A chimera protein derived from the bacterial pore-forming toxin intermedilysin (His-LTBP-CDC(ss)(IP)) forms the basis for a novel DDS tool.
Department of Biological Science and Technology, Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Tokushima, Japan.
Atsushi
A
Tabata
Yukimasa
Y
Ohkubo
Eriko
E
Sakakura
Toshifumi
T
Tomoyasu
Kazuto
K
Ohkura
Hideaki
H
Nagamune
D001430:Bacteriocins / Q000008:administration & dosage* / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008081:Liposomes; D008856:Microscopy, Fluorescence; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000138:chemical synthesis
D001430:Bacteriocins; D008081:Liposomes; D011993:Recombinant Fusion Proteins; C403910:intermedilysin protein, Streptococcus intermedius