Novel nucleoside diphosphatase contributes to Staphylococcus aureus virulence

Kenta Imae, Yuki Saito, Hayato Kizaki, Hiroki Ryuno, Han Mao, Atsushi Miyashita, Yutaka Suzuki, Kazuhisa Sekimizu, Chikara Kaito

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5 Citations (Scopus)

Abstract

We identified SA1684 as a Staphylococcus aureus virulence gene using a silkworm infection model. The SA1684 gene product carried the DUF402 domain, which is found in RNA-binding proteins, and had amino acid sequence similarity with a nucleoside diphosphatase, Streptomyces coelicolor SC4828 protein. The SA1684-deletion mutant exhibited drastically decreased virulence, in which the LD50 against silkworms was more than 10 times that of the parent strain. The SA1684-deletion mutant also exhibited decreased exotoxin production and colony-spreading ability. Purified SA1684 protein had Mn2+- or Co2+-dependent hydrolyzing activity against nucleoside diphosphates. Alanine substitutions of Tyr-88, Asp-106, and Asp-123/Glu-124, which are conserved between SA1684 and SC4828, diminished the nucleoside diphosphatase activity. Introduction of the wild-type SA1684 gene restored the hemolysin production of the SA1684-deletion mutant, whereas none of the alanine-substituted SA1684 mutant genes restored the hemolysin production. RNA sequence analysis revealed that SA1684 is required for the expression of the virulence regulatory genes agr, sarZ, and sarX, as well as metabolic genes involved in glycolysis and fermentation pathways. These findings suggest that the novel nucleoside diphosphataseSA1684links metabolic pathways and virulence gene expression and plays an important role in S. aureus virulence.

Original languageEnglish
Pages (from-to)18608-18619
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number36
DOIs
Publication statusPublished - 2016 Sep 2
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Imae, K., Saito, Y., Kizaki, H., Ryuno, H., Mao, H., Miyashita, A., Suzuki, Y., Sekimizu, K., & Kaito, C. (2016). Novel nucleoside diphosphatase contributes to Staphylococcus aureus virulence. Journal of Biological Chemistry, 291(36), 18608-18619. https://doi.org/10.1074/jbc.M116.721845