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1.
J Biol Chem ; 276(4): 2658-67, 2001 Jan 26.
Article in English | MEDLINE | ID: mdl-11160124

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 up-regulate 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.


Subject(s)
Carrier Proteins/metabolism , Phosphoproteins/metabolism , RNA, Antisense/metabolism , RNA, Bacterial/metabolism , Staphylococcus aureus/pathogenicity , Adaptor Proteins, Signal Transducing , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Base Sequence , Gene Expression Regulation, Bacterial , Models, Biological , Molecular Sequence Data , Phosphoproteins/genetics , Phosphorylation , Signal Transduction
2.
Science ; 280(5362): 438-40, 1998 Apr 17.
Article in English | MEDLINE | ID: mdl-9545222

ABSTRACT

Staphylococcus aureus causes pathologies ranging from minor skin infections to life-threatening diseases. Pathogenic effects are largely due to production of bacterial toxin, which is regulated by an RNA molecule, RNAIII. The S. aureus protein called RAP (RNAIII activating protein) activates RNAIII, and a peptide called RIP (RNAIII inhibiting peptide), produced by a nonpathogenic bacteria, inhibits RNAIII. Mice vaccinated with RAP or treated with purified or synthetic RIP were protected from S. aureus pathology. Thus, these two molecules may provide useful approaches for the prevention and treatment of diseases caused by S. aureus.


Subject(s)
Bacterial Proteins/immunology , Bacterial Vaccines , Oligopeptides/therapeutic use , Staphylococcal Skin Infections/drug therapy , Staphylococcal Skin Infections/prevention & control , Staphylococcus aureus/pathogenicity , Amino Acid Sequence , Animals , Antibodies, Bacterial/biosynthesis , Bacterial Proteins/antagonists & inhibitors , Bacterial Proteins/isolation & purification , Bacterial Toxins/biosynthesis , Male , Mice , Mice, Hairless , Oligopeptides/isolation & purification , RNA, Antisense/genetics , RNA, Bacterial/genetics , Signal Transduction , Staphylococcal Skin Infections/immunology , Staphylococcus aureus/metabolism , Vaccination , Virulence
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