Anti-microbial defensin-related peptides and methods of use

Abstract

An antimicrobial peptide and its analogs that are insensitive to physiological salt and divalent cation concentrations is provided, as are methods for their use to treat and prevent bacterial infections. The peptides are especially useful to treat infections caused by bacteria that are resistant to traditional antibiotic therapy.

1 . Substantially purified peptides having an amino acid sequence represented by a sequence selected from the group consisting of: 
       
         
           
                 
                 
                 
               
                   LRVRRTLQCSCRRVCRNTCSCIRLSRS TYAS; 
                   (SEQ ID NO: 1) 
                     
                 
                     
                 
                   LQCSCRRVCRNTCSCIRLSRSTYAS; 
                   (SEQ ID NO: 2) 
                 
                     
                 
                   LRVRRTLQCSCRRVCRNTCSCI; 
                   (SEQ ID NO: 3) 
                 
                     
                 
                   LRVRRTLQCSCRRVCRNTCSCIRLSR; 
                   (SEQ ID NO: 4) 
                 
                     
                 
                   LQCSCRRVCRNTCSCI; 
                   (SEQ ID NO: 5) 
                 
                   and 
                 
                     
                 
                   LRVRRTLQASARRVARNTASAIRLSRSTYAS 
                   (SEQ ID NO: 6) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . An antibacterial composition active under physiological conditions, comprising one or more peptides with an amino acid sequence represented by a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6. 
     
     
         3 . The antibacterial composition of  claim 2 , wherein a salt concentration of said antimicrobial composition is in the range of from 0 to 250 mM salt. 
     
     
         4 . The antibacterial composition of  claim 3 , wherein said salt is NaCl or KCl, or both. 
     
     
         5 . The antibacterial composition of  claim 3 , wherein said salt concentration is at least 50 mM. 
     
     
         6 . The antibacterial composition of  claim 2 , wherein a divalent cation concentration of said antimicrobial composition is in the range of from 0 to 5 mM. 
     
     
         7 . The antibacterial composition of  claim 6 , wherein said divalent cation is Mg +2  or Ca +2 , or both. 
     
     
         8 . The antibacterial composition of  claim 6 , wherein said divalent cation concentration is at least 1 mM. 
     
     
         9 . A method for killing bacteria at a location having a salt concentration in the range of from 0 to 250 mM or a divalent cation concentration in the range of from 0 to 5 mM, comprising the step of
 exposing said bacteria to one or more peptides with an amino acid sequence represented by a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6,   
       wherein said step of exposing kills said bacteria. 
     
     
         10 . The method of  claim 9 , wherein said bacteria are antibiotic-resistant bacteria. 
     
     
         11 . The method of  claim 9 , wherein said location is in vivo. 
     
     
         12 . The method of  claim 9 , wherein said location is a circulatory, respiratory, digestive, or reproductive system of a patient. 
     
     
         13 . The method of  claim 9 , wherein said location is an open wound. 
     
     
         14 . The method of  claim 9 , wherein said salt concentration is at least 50 mM. 
     
     
         15 . The method of  claim 9 , wherein said divalent cation concentration is at least 1 mM. 
     
     
         16 . A method for treating or preventing a bacterial infection in a patient in need thereof, comprising the steps of
 providing to said patient a composition comprising one or more peptides with an amino acid sequence represented by a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, and   allowing said peptides to contact bacteria under physiological conditions in order to ameliorate or prevent said bacterial infection.   
     
     
         17 . The method of  claim 16 , wherein provision is systemic. 
     
     
         18 . The method of  claim 16 , wherein provision is topical.