A Novel Peptide Screened by Phage Display Can Mimic TRAP Antigen Epitope against Staphylococcus aureus Infections*

Staphylococcus aureus is a major human pathogen. Pathogenic effects are largely due to production of bacterial toxins, whose synthesis is controlled by an mRNA molecule termed RNAIII. The S. aureus protein called RAP (RNAIII-activating protein) is secreted and activates RNAIII production by inducing the phosphorylation of its target protein TRAP (target of RAP). Antibodies to TRAP have been shown to suppress exotoxin production by S. aureus in vitro, suggesting that TRAP may be a useful vaccine target site. Here we showed that a peptide TA21 was identified by screening a phage display library using anti-TRAP antibodies. Mice vaccinated with Escherichia coli engineered to express TA21 on their surface (FTA21) were protected from S. aureus infections, using sepsis and cellulitis mice models. By sequence analysis, it was found that the TA21 is highly homologous to the C-terminal sequence of TRAP which is conserved among S. aureus and Staphylococcus epidermidis, suggesting that peptide TA21 may be a useful broad vaccine to protect from infection caused by various staphylococcal strains.

[1]  F. Lowy Staphylococcus aureus infections. , 2009, The New England journal of medicine.

[2]  V. Saba,et al.  Suppression of drug-resistant Staphylococcal Infections by the quorum-sensing inhibitor RNAIII-inhibiting peptide. , 2004, The Journal of infectious diseases.

[3]  I. Borovok,et al.  Quorum Sensing in Staphylococci Is Regulated via Phosphorylation of Three Conserved Histidine Residues* , 2004, Journal of Biological Chemistry.

[4]  Shanru Li,et al.  Inhibition of Staphylococcus aureus pathogenesis in vitro and in vivo by RAP-binding peptides , 2003, Peptides.

[5]  E. Medina-Acosta,et al.  Treatment efficacy of the lead RNAIII-inhibiting peptide YSPWTNF-NH2 in acquired Staphylococcus aureus sepsis: a histopathological assessment , 2003, Peptides.

[6]  Saul Tzipori,et al.  Characterization of RAP, a quorum sensing activator of Staphylococcus aureus. , 2003, FEMS microbiology letters.

[7]  V. Saba,et al.  Use of the quorum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staphylococcus epidermidis. , 2003, The Journal of infectious diseases.

[8]  E. Medina-Acosta,et al.  RNAIII inhibiting peptide (RIP) inhibits agr-regulated toxin production , 2001, Peptides.

[9]  M. Otto Staphylococcus aureus and Staphylococcus epidermidis peptide pheromones produced by the accessory gene regulator agr system , 2001, Peptides.

[10]  M. Hirshberg,et al.  Regulation of Staphylococcus aureus Pathogenesis via Target of RNAIII-activating Protein (TRAP)* , 2001, The Journal of Biological Chemistry.

[11]  R. Rasooly,et al.  Autoinducer of virulence as a target for vaccine and therapy against Staphylococcus aureus. , 1998, Science.

[12]  A. Folgori,et al.  Induction of anti‐carbohydrate antibodies by phage library‐selected peptide mimics , 1997, European journal of immunology.

[13]  T. Ternynck,et al.  Mimotopes of polyreactive anti‐DNA antibodies identified using phage‐display peptide libraries , 1997, European journal of immunology.

[14]  G. Ossenkoppele,et al.  A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. , 1994, Journal of immunological methods.

[15]  J. Kornblum,et al.  Synthesis of staphylococcal virulence factors is controlled by a regulatory RNA molecule. , 1993, The EMBO journal.