Regulation of Staphylococcus aureus Pathogenesis via Target of RNAIII-activating Protein (TRAP)

Naomi Balaban, Tzipora Goldkorn, Yael Gov, Miriam Hirshberg, Nir Koyfman, Harry R. Matthews, Rachael T. Nhan, Baljit Singh, Orit Uziel

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Staphylococcus aureus can cause disease through the production of toxins. Toxin production is autoinduced by the protein RNAIII-activating protein (RAP) and by the autoinducing peptide (AIP), and is inhibited by RNAIII-inhibiting peptide (RIP) and by inhibitory AIPs. RAP has been shown to be a useful vaccine target site, and RIP and inhibitory AIPs as therapeutic molecules to prevent and suppress S. aureus infections. Development of therapeutic strategies based on these molecules has been hindered by a lack of knowledge of the molecular mechanisms by which they activate or inhibit virulence. Here, we show that RAP specifically induces the phosphorylation of a novel 21-kDa protein, whereas RIP inhibits its phosphorylation. This protein was termed target of RAP (TRAP). The synthesis of the virulence regulatory molecule, RNAIII, is not activated by RAP in the trap mutant strain, suggesting that RAP activates RNAIII synthesis via TRAP. Phosphoamino acid analysis shows that TRAP is histidine-phosphorylated, suggesting that TRAP may be a sensor of RAP. AIPs upregulate the synthesis of RNAIII also in trap mutant strains, suggesting that TRAP and AIPs activate RNAIII synthesis via distinct signal transduction pathways. Furthermore, TRAP phosphorylation is down-regulated in the presence of AIP, suggesting that a network of signal transduction pathways regulate S. aureus pathogenesis.

Original languageEnglish (US)
Pages (from-to)2658-2667
Number of pages10
JournalJournal of Biological Chemistry
Volume276
Issue number4
StatePublished - Jan 26 2001

ASJC Scopus subject areas

  • Biochemistry

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    Balaban, N., Goldkorn, T., Gov, Y., Hirshberg, M., Koyfman, N., Matthews, H. R., Nhan, R. T., Singh, B., & Uziel, O. (2001). Regulation of Staphylococcus aureus Pathogenesis via Target of RNAIII-activating Protein (TRAP). Journal of Biological Chemistry, 276(4), 2658-2667.