RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis: Structure and function analysis

Yael Gov, Arkady Bitler, Giorgo Dell'Acqua, Jose V Torres, Naomi Balaban

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Staphylococcus aureus are gram-positive bacteria that can cause serious diseases in humans and animals. S. aureus infections can be prevented by the heptapeptide RNAIII inhibiting peptide (RIP). RIP was originally isolated from culture supernatants of coagulase negative staphylococci presumed to be S. xylosus. The sequence of RIP was identified as YSPXTNF. Native RIP and its synthetic analogue YSPWTNF have been shown to be effective inhibitors of diseases caused by various strains of S. aureus, including, cellulitis, keratitis, septic arthritis, osteomylitis and mastitis. RIP is therefore considered to be a global inhibitor of S. aureus. We show here that: 1) the amide form of RIP (YSPWTNF-NH2) is highly stable and is therefore the one recommended for use. 2) RIP inhibits S. aureus pathogenesis by inhibiting the synthesis of both agr transcripts RNAII and RNAIII. 3) Although RIP inhibits agr, it also reduces bacterial adherence to mammalian cells and to plastic (tested on HEp2 cells and on polystyrene by fluorescence and atomic force microscopy), suggesting that RIP can be used safely as a therapeutic molecule. 4) RIP derivatives were designed and tested for their ability to inhibit RNAIII in vitro and cellulitis in vivo. Not all peptides that inhibited RNAIII also inhibited an infection in vivo, indicating that studies must be carried out in vivo before considering a peptide to be of therapeutic potential. 5) The RIP derivative containing Lysine and Isoleucine at positions 2 and 4, respectively, inhibited S. aureus infections in vivo (tested on cellulitis), suggesting that both RIP YSPWTNF and its derivative YKPITNF are effective inhibitors of infections caused by S. aureus.

Original languageEnglish (US)
Pages (from-to)1609-1620
Number of pages12
JournalPeptides
Volume22
Issue number10
DOIs
StatePublished - 2001

Fingerprint

Staphylococcus aureus
Cellulitis
Infection
Derivatives
RNAIII inhibiting peptide
Peptides
Infectious Arthritis
Keratitis
Mastitis
Isoleucine
Atomic Force Microscopy
Coagulase
Polystyrenes
Gram-Positive Bacteria
Staphylococcus
Amides
Plastics
Lysine
Atomic force microscopy
Bacteria

Keywords

  • Adhesion
  • agr
  • Atomic force microscopy
  • Bacterial virulence
  • Quorum sensing
  • RAP
  • RIP
  • Staphylococcus aureus
  • Synthetic peptide inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

Cite this

RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis : Structure and function analysis. / Gov, Yael; Bitler, Arkady; Dell'Acqua, Giorgo; Torres, Jose V; Balaban, Naomi.

In: Peptides, Vol. 22, No. 10, 2001, p. 1609-1620.

Research output: Contribution to journalArticle

Gov, Yael ; Bitler, Arkady ; Dell'Acqua, Giorgo ; Torres, Jose V ; Balaban, Naomi. / RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis : Structure and function analysis. In: Peptides. 2001 ; Vol. 22, No. 10. pp. 1609-1620.
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T1 - RNAIII inhibiting peptide (RIP), a global inhibitor of Staphylococcus aureus pathogenesis

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AU - Bitler, Arkady

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