Methods and Compositions for the Treatment and Prevention of Staphylococcus Infections

Abstract

A biologically pure RNAIII inhibiting peptide (RIP), that includes five contiguous amino acids of the sequence YX 2 PX 1 TNF, where X 1 is C, W, I or a modified amino acid, and X 2 is K or S is provided. The RIP further includes amino acids having a sequence that differs from the sequence YX 2 PX 1 TNF by two substitutions or deletions, where X 1 is C, W, I or a modified amino acid, and X 2 is K or S. The RIP does not consist of the sequence YSPX 1 TNF, where X 1 is C, W, I or a modified amino acid. This agent offers improved protection against and treatment of staphylococcal infections, and related bacteria infections, in mammals.

1 . A biologically pure RNAIII inhibiting peptide (RIP), comprising:
 (a) five contiguous amino acids of the sequence YX 2 PX 1 TNF, where X 1  is C, W, I or a modified amino acid, and X 2  is K or S; or   (b) amino acids having a sequence that differs from the sequence YX 2 PX 1 TNF by two substitutions or deletions, where X 1  is C, W, I or a modified amino acid, and X 2  is K or S,   where the RIP does not consist of the sequence YSPX 2 TNF, where X 1  is C, W, I, or a modified amino acid.   
     
     
         2 . The RIP of  claim 1 , comprising the amino acids having a sequence that differs from the sequence YX 2 PX 1 TNF by one substitution or deletion, where X 1  is C, W, I or a modified amino acid, and X 2  is K or S. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The RIP of  claim 1 , comprising the sequence PCTNF. 
     
     
         7 - 9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising RNAIII inhibiting peptide (RIP) that comprises:
 (a) five contiguous amino acids of the sequence YX 2 PX 1 TNF, where X 1  is C, W, I or a modified amino acid, and X 2  is K or S; or   (b) amino acids having a sequence that differs from the sequence YX 2 PX 1 TNF by two substitutions or deletions, where X 1  is C, W, I or a modified amino acid, and X 2  is K or S,   where the RIP does not consist of the sequence YSPX 2 TNF, where X 1  is C, W, I, or a modified amino acid, and   where the RIP is in an amount effective to treat or reduce the risk of bacterial infection in a mammalian individual receiving said composition.   
     
     
         11 . The pharmaceutical composition of  claim 10 , where the RIP is biologically pure. 
     
     
         12 . The pharmaceutical composition of  claim 10 , where the RIP is capable of prophylactically preventing a staphylococcus infection. 
     
     
         13 . The pharmaceutical composition of  claim 10 , where the RIP is capable of being used therapeutically after the onset of symptoms of staphylococcus infections. 
     
     
         14 . The pharmaceutical composition of  claim 10 , where the RIP comprises about 0.1% to 50% by weight of the composition. 
     
     
         15 . The pharmaceutical composition of  claim 10 , where the RIP comprises about 2% to 20% by weight of the composition. 
     
     
         16 . The pharmaceutical composition of  claim 10 , where the composition is formulated for topical, oral, intravenous, intraperitoneal, intramuscular, transdermal, nasal, or iontophoretic administration. 
     
     
         17 . The composition of  claim 10  where the composition is formulated for topical administration. 
     
     
         18 . The composition of  claim 10 , where the composition further comprises liposomes. 
     
     
         19 . The composition of  claim 10 , where the composition is formulated as a depot-style system, an encapsulated form, or an implant. 
     
     
         20 . The composition of  claim 10 , further comprising an anti-microbial agent.