Thermostable direct hemolysin of Vibrio parahaemolyticus is a bacterial reversible amyloid toxin

Takashi Fukui, Kentaro Shiraki, Daizo Hamada, Kojiro Hara, Tomoko Miyata, Shinsuke Fujiwara, Kouta Mayanagi, Keiko Yanagihara, Tetsuya Iida, Eiichiro Fukusaki, Tadayuki Imanaka, Takeshi Honda, Itaru Yanagihara

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20 Citations (Scopus)

Abstract

Thermostable direct hemolysin (TDH), a major virulence factor of Vibrio parahaemolyticus, is detoxified by heating at ∼60-70 °C but is reactivated by additional heating above 80 °C. This paradoxical phenomenon, known as the Arrhenius effect, has remained unexplained for ∼100 years. We now demonstrate that the effect is related to structural changes in the protein that produce fibrils. The native TDH (TDHn) is transformed into nontoxic fibrils rich in β-strands by incubation at 60 °C (TDHi). The TDHi fibrils are dissociated into unfolded states by further heating above 80 °C (TDHu). Rapid cooling of TDHu results in refolding of the protein into toxic TDHn, whereas the protein is trapped in the TDHi structure by slow cooling of TDHu. Transmission electron microscopy indicates the fibrillar structures of TDHi. The fibrils show both the property of the nucleation-dependent elongation and the increase in its thioflavin T fluorescence. Formation of β-rich structures of TDH was also observed in the presence of lipid vesicles containing ganglioside GT1b, a putative TDH receptor. Congo red was found to inhibit the hemolytic activity of TDH in a dose-dependent manner. These data reveal that the mechanism of the Arrhenius effect which is tightly related to the fibrillogenicity of TDH.

Original languageEnglish
Pages (from-to)9825-9832
Number of pages8
JournalBiochemistry
Volume44
Issue number29
DOIs
Publication statusPublished - Jul 26 2005

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Fukui, T., Shiraki, K., Hamada, D., Hara, K., Miyata, T., Fujiwara, S., Mayanagi, K., Yanagihara, K., Iida, T., Fukusaki, E., Imanaka, T., Honda, T., & Yanagihara, I. (2005). Thermostable direct hemolysin of Vibrio parahaemolyticus is a bacterial reversible amyloid toxin. Biochemistry, 44(29), 9825-9832. https://doi.org/10.1021/bi050311s