High dose of antibiotic colistin induces oligomerization of molecular chaperone HSP90

Shuntaro Togashi, Kyosuke Takahashi, Arisa Tamura, Ikumi Toyota, Shiori Hatakeyama, Atsushi Komatsuda, Ikuru Kudo, Erina Sasaki Kudoh, Tomoya Okamoto, Asami Haga, Asuka Miyamoto, Ewa Grave, Taku Sugawara, Hiroaki Shimizu, Hideaki Itoh

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Colistin is an antimicrobial cationic peptide that belongs to the polymyxin family. Colistin was clinically used for the treatment of gram-negative infections but fell out of favour because of its significant side effects including neurotoxicity and nephrotoxicity. More recently, colistin has been regarded as one of the important options for nosocomial infections caused by multidrug resistant bacteria. Mechanisms of both the side effect onset of the drug and the side effect reduction are yet to be elucidated. In this study, we identified the specific binding protein of colistin using an affinity column chromatography. Colistin binds to the molecular chaperone HSP90. Although colistin slightly suppressed the chaperone activity of HSP90, there are no effects on the ATPase activity for a low concentration of colistin. Interestingly, colistin-induced aggregation of HSP90 via the Ndomain. As for the cell viability of the SHSY5Y cell, the cell viability decreased to approximately 80% by the colistin 300μM. However, the cell viability recovered to approximately 100% by adding ATP dosage. The same result was obtained by dot blot assay using anti-HSP90 antibody. Our results may help to understand the side effect mechanism of colistin.

Original languageEnglish
Pages (from-to)27-36
Number of pages10
JournalJournal of Biochemistry
Volume162
Issue number1
DOIs
Publication statusPublished - Jul 1 2017
Externally publishedYes

Keywords

  • antibiotics
  • Colistin
  • HSP90
  • Molecular chaperone
  • polymixin.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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  • Cite this

    Togashi, S., Takahashi, K., Tamura, A., Toyota, I., Hatakeyama, S., Komatsuda, A., Kudo, I., Sasaki Kudoh, E., Okamoto, T., Haga, A., Miyamoto, A., Grave, E., Sugawara, T., Shimizu, H., & Itoh, H. (2017). High dose of antibiotic colistin induces oligomerization of molecular chaperone HSP90. Journal of Biochemistry, 162(1), 27-36. https://doi.org/10.1093/jb/mvw104