Blocking expression of virulence factors in S. aureus

Abstract

This invention provides peptides which inhibit agr transcription in S. aureus and thereby block the expression of virulence factors in S. aureus , pharmaceutical compositions comprising these peptides, as well as methods for treating or preventing an infection or disease caused by S. aureus using the peptides of the present invention.

What is claimed is:  
     
         1 . A purified peptide which inhibits agr-rnaIII transcription in  S. aureus , said peptide containing six to twelve amino acids in length and comprising amino acid number 28 from the AgrD region of a staphylococci bacterium, or an analogue thereof which inhibits agr-rnaIII transcription in  S. aureus.    
     
     
         2 . The peptide of  claim 1 , wherein the staphylococci bacterium is selected from the group consisting of  S. aureus, S. capitis, S. caprae, S. carnosus, S. caseolyticus, S. epidermidis, S. haemolyticus, S. hominis, S. hyicus  subsp.  hyicus, S. hyicus  subsp.  chromo, S. kloosii, S. lentus, S. lugdunensis, S. sciuri, S. simulans  and  S. xylosus.    
     
     
         3 . The peptide of  claim 2 , wherein the staphylococci bacterium is S. lugdunensis.  
     
     
         4 . The peptide of  claim 3 , having the amino acid sequence NH 2 -Asp-Ile-Cys-Asn-Ala-Tyr-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         5 . The peptide of  claim 2 , wherein the staphylococci bacterium is  S. aureus.    
     
     
         6 . The peptide of  claim 5  having the amino acid sequence NH 2 -Tyr-Ser-Thr-Cys-Asp-Phe-Ile-Met-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         7 . The peptide of  claim 5  having the amino acid sequence NH 2 -Gly-Val-Asn-Ala-Cys-Ser-Ser-Leu-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         8 . The peptide of  claim 5  having the amino acid sequence NH 2 -Tyr-Ile-Asn-Cys-Asp-Phe-Leu-Leu-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         9 . A peptide composition comprising a peptide which inhibits agr-rnaIII transcription in  S. aureus  and a pharmaceutically acceptable carrier, wherein said peptide contains six to twelve amino acids in length and comprises amino acid number 28 from the AgrD region of a staphylococci bacterium, or an analogue thereof which inhibits agr-rnaIII transcription in  S. aureus.    
     
     
         10 . The peptide composition of  claim 5 , wherein the staphylococci bacterium is selected from the group consisting of  S. aureus, S. capitis, S. caprae, S. carnosus, S. caseolyticus, S. epidermidis, S. haemolyticus, S. hominis, S. hyicus  subsp.  hyicus, S. hyicus  subsp.  chromo, S. kloosii, S. lentus, S. lugdunensis, S. sciuri, S. simulans  and  S. xylosus.    
     
     
         11 . The peptide composition of  claim 10 , wherein the staphylococci bacterium is  S. lugdunensis.    
     
     
         12 . The peptide composition of  claim 11 , wherein the peptide has the amino acid sequence NH 2 -Asp-Ile-Cys-Asn-Ala-Tyr-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         13 . The peptide composition of  claim 10 , wherein the staphylococci bacterium is  S. aureus.    
     
     
         14 . The peptide composition of  claim 13 , wherein the peptide has the amino acid sequence NH 2 -Tyr-Ser-Thr-Cys-Asp-Phe-Ile-Met-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         15 . The peptide composition of  claim 13 , wherein the peptide has the amino acid sequence NH 2 -Gly-Val-Asn-Ala-Cys-Ser-Ser-Leu-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         16 . The peptide composition of  claim 13 , wherein the peptide has the amino acid sequence NH 2 -Tyr-Ile-Asn-Cys-Asp-Phe-Leu-Leu-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         17 . A method for treating or preventing an infection or disease caused by  S. aureus  in a subject comprising administering to the subject a peptide which inhibits agr-rnaIII transcription in  S. aureus  in an amount effective to treat or prevent the infection or disease caused by  S. aureus , wherein said peptide contains six to twelve amino acids in length and comprises amino acid number 28 from the AgrD region of a staphylococci bacterium, or an analogue thereof which inhibits agr-rnaIII transcription in  S. aureus.    
     
     
         18 . The method of  claim 17 , wherein the staphylococci bacterium is selected from the group consisting of  S. aureus, S. capitis, S. caprae, S. carnosus, S. caseolyticus, S. epidermidis, S. haemolyticus, S. hominis, S. hyicus  subsp.  hyicus, S. hyicus  subsp.  chromo, S. kloosii, S. lentus, S. lugdunensis, S. sciuri, S. simulans  and  S. xylosus.    
     
     
         19 . The method of  claim 18 , wherein the staphylococci bacterium is  S. lugdunensis.    
     
     
         20 . The method of  claim 19 , wherein the peptide has the amino acid sequence NH 2 -Asp-Ile-Cys-Asn-Ala-Tyr-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         21 . The method of  claim 18 , wherein the staphylococci bacterium is  S. aureus.    
     
     
         22 . The method of  claim 21 , wherein the peptide has the amino acid sequence NH 2 -Tyr-Ser-Thr-Cys-Asp-Phe-Ile-Met-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         23 . The method of  claim 21 , wherein the peptide has the amino acid sequence NH 2 -Gly-Val-Asn-Ala-Cys-Ser-Ser-Leu-Phe-COOH and a cyclic thioester bond between Cys and COOH.  
     
     
         24 . The method of  claim 21 , wherein the peptide has the amino acid sequence NH 2 -Tyr-Ile-Asn-Cys-Asp-Phe-Leu-Leu-COOH and a cyclic thioester bond between Cys and COOH.