Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin
1
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
2
Division of Molecular Biology, Institute for Health Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770-8514, Japan
*
Author to whom correspondence should be addressed.
Toxins 2018, 10(5), 209; https://doi.org/10.3390/toxins10050209
Received: 21 April 2018 / Revised: 14 May 2018 / Accepted: 18 May 2018 / Published: 20 May 2018
(This article belongs to the Special Issue Bacterial Pore-Forming Toxins)
Clostridium perfringens iota-toxin is a binary actin-ADP-ribosylating toxin composed of the enzymatic component Ia and receptor binding component Ib. Ib binds to a cell surface receptor, forms Ib oligomer in lipid rafts, and associates with Ia. The Ia-Ib complex then internalizes by endocytosis. Here, we showed that acid sphingomyelinase (ASMase) facilitates the cellular uptake of iota-toxin. Inhibitions of ASMase and lysosomal exocytosis by respective blockers depressed cell rounding induced by iota-toxin. The cytotoxicity of the toxin increased in the presence of Ca2+ in extracellular fluids. Ib entered target cells in the presence but not the absence of Ca2+. Ib induced the extracellular release of ASMase in the presence of Ca2+. ASMase siRNA prevented the cell rounding induced by iota-toxin. Furthermore, treatment of the cells with Ib resulted in the production of ceramide in cytoplasmic vesicles. These observations showed that ASMase promotes the internalization of iota-toxin into target cells.
View Full-Text
▼
Show Figures
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Nagahama, M.; Takehara, M.; Miyamoto, K.; Ishidoh, K.; Kobayashi, K. Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin. Toxins 2018, 10, 209.
AMA Style
Nagahama M, Takehara M, Miyamoto K, Ishidoh K, Kobayashi K. Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin. Toxins. 2018; 10(5):209.
Chicago/Turabian StyleNagahama, Masahiro; Takehara, Masaya; Miyamoto, Kazuaki; Ishidoh, Kazumi; Kobayashi, Keiko. 2018. "Acid Sphingomyelinase Promotes Cellular Internalization of Clostridium perfringens Iota-Toxin" Toxins 10, no. 5: 209.
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
Search more from Scilit