Methods and compositions for the treatment and prevention of staphylococcus and other bacterial infections

Abstract

The invention features methods and compositions for treatment or prevention of infection by, or disease caused by infection with, certain species of bacteria, including in particular bacteria in which a RAP-type and/or TRAP-type molecule plays a role in pathogenesis. This includes Staphylococcus species.

1 . A method of treating or reducing the risk of a bacterial infection comprising administering to a subject a pharmaceutical composition comprising an amount of an RNAIII inhibiting peptide (RIP) effective to treat or reduce the risk of a bacterial infection.  
     
     
         2 . The method of  claim 1 , where the RIP 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,    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, or    c) amino acids having a sequence YX 2 PX 1 TNF, where X 1  is not C, W or I and X 2  is K or S.    
     
     
         3 . The method of  claim 2 , where X 2  is K.  
     
     
         4 . The method of  claim 2 , where the RIP comprises the amino acid sequence IKKYX 2 PX 1 TNF, where X 1  is C, W, I or a modified amino acid and X 2  is K or S.  
     
     
         5 . The method of  claim 2 , where the RIP comprises amino acids having a sequence that differs from the sequence YSPX 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.  
     
     
         6 . The method of  claim 1 , where the bacterial infection is caused by  Staphylococcus  spp.,  S. aureus, S. epidermidis, Bacillus  spp.,  B. subtilus, B. cereus, B. anthracis, Listeria  spp.,  L. innocua, L. monoctogenes, Streptococcus pyogenes, Lactococcus lactis, Enterococcus faecalis, Escherichia coli , or  Clostridium acetobtylicum.    
     
     
         7 . The method of  claim 1 , where the RIP is biologically pure.  
     
     
         8 . The method of  claim 1 , where the RIP comprises about 0.1% to 50% by weight of the composition.  
     
     
         9 . The method of  claim 1 , where the RIP comprises about 2% to 20% by weight of the composition.  
     
     
         10 . The method of  claim 1 , where the administering is by a topical, oral, intravenous, intraperitoneal, intramuscular, transdermal, nasally, or iontophoretic route.  
     
     
         11 . The method of  claim 10 , where the administration is by a topical route.  
     
     
         12 . The method of  claim 1 , where the pharmaceutical composition further comprises liposomes.  
     
     
         13 . The method of  claim 1 , where the pharmaceutical composition is delivered in a depot-style system, an encapsulated form, or an implant.  
     
     
         14 . The method of  claim 1 , further comprising administering anti-microbial therapy to the subject, where the combined administration of the pharmaceutical composition and anti-microbial therapy treats or reduces the risk of a bacterial infection.  
     
     
         15 . The method of  claim 1 , where the subject is a human.  
     
     
         16 . The method of  claim 1 , where the subject is an animal.