Antimicrobial peptides and methods of use thereof

Abstract

Aspects of the present invention relate to peptides having antimicrobial activity. In certain aspects, the invention relates to peptides having potent antimicrobial activity, broad-spectrum antimicrobial activity, and/or the ability to kill otherwise antibiotic-resistant microbes, or microbes protected by biofilms.

1 . An antimicrobial composition comprising an antimicrobial peptide, wherein the antimicrobial peptide is 35 amino acid residues or less in length and comprises an amphipathic region having an amino acid sequence according to Formula 1 or 2: 
       
         
           
                 
                 
               
                     
                   XYYXXYYXXYXXYYXXYY (Formula 1) 
                 
                     
                     
                 
                     
                   YYXXYYXXYXXYYXXYYX (Formula 2) 
                 
             
                
                
                
               
            
           
         
       
       wherein:
 each Y is a hydrophobic residue; 
 each X is independently a hydrophilic amino acid residue. 
 
     
     
         2 . The antimicrobial composition of  claim 1 , wherein the antimicrobial peptide is effective in killing at least one bacterial, fungal, or protozoan organism. 
     
     
         3 .- 5 . (canceled) 
     
     
         6 . The antimicrobial composition of  claim 1 , wherein the antimicrobial peptide comprises an amphipathic region having a cationic surface that binds to the membrane of a microbial pathogen. 
     
     
         7 . The antimicrobial composition of  claim 1 , wherein the antimicrobial peptide comprises an amino acid sequence selected from RP-443 and RP-444 (SEQ ID NOs: 22-23). 
     
     
         8 . The antimicrobial composition of  claim 1 , wherein the antimicrobial peptide further comprises a hydrophobic tail region on the N-terminus, C-terminus, or both, wherein the hydrophobic tail region has a sequence of from 4 to 10 hydrophobic amino acids. 
     
     
         9 . The antimicrobial composition of  claim 8 , wherein the hydrophobic tail region comprises the amino acid sequence set forth in SEQ ID NO: 4. 
     
     
         10 . An antimicrobial composition comprising an antimicrobial peptide, wherein the antimicrobial peptide is 35 amino acid residues or less in length and comprises two amphipathic regions joined together by a linker comprising a bubble region of Formula 5: 
       
         
           
                 
                 
               
                     
                   C(Y/X)(Y/X)(Y/X)(Y/X)C 
                 
             
                
               
            
           
         
       
       wherein:
 each Y is a hydrophobic residue; 
 each X is independently a hydrophilic amino acid residue. 
 
     
     
         11 . The antimicrobial composition of  claim 10 , wherein the two amphipathic regions are each 5 or more residues in length and consist of an alternating sequence of one hydrophobic (Y) amino acid residue and one hydrophilic amino acid residue (X). 
     
     
         12 . The antimicrobial composition of  claim 11 , wherein the bubble region comprises the sequence CLGRFC (SEQ ID NO: 7). 
     
     
         13 . (canceled) 
     
     
         14 . The antimicrobial composition of  claim 10 , wherein the two amphipathic regions have the same amino acid sequence. 
     
     
         15 . The antimicrobial composition of  claim 10 , wherein the two amphipathic regions have different amino acid sequences. 
     
     
         16 . The antimicrobial composition of  claim 10 , wherein the antimicrobial peptide comprises an amino acid sequence RP-504 (SEQ ID NO: 27). 
     
     
         17 . A pharmaceutical composition comprising the antimicrobial composition of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         18 . (canceled) 
     
     
         19 . The pharmaceutical composition of  claim 17 , wherein the composition is formulated for oral administration and further comprises an enteric coating. 
     
     
         20 . The pharmaceutical composition of  claim 17 , wherein the composition is formulated for topical delivery in a form selected from a gel suspension, a cream, microneedle, and infused into a bandage or topical patch. 
     
     
         21 . The pharmaceutical composition of  claim 17 , further comprising an additional bioactive agent. 
     
     
         22 . The pharmaceutical composition of  claim 21 , wherein the additional bioactive agent is selected from an antimicrobial agent, an anti-inflammatory drug, an anti-nausea drug, an anti-pain medication, and combinations thereof. 
     
     
         23 . The pharmaceutical composition of  claim 17 , wherein the composition is formulated to be coated on the surface of an implantable medical device. 
     
     
         24 . (canceled) 
     
     
         25 . A method of treating or preventing a microbial infection in a subject in need thereof, the method comprising administering a pharmaceutical composition according to  claim 1  to the subject. 
     
     
         26 . The method of  claim 25 , wherein the pharmaceutical composition is administered to the subject orally, parenterally, or topically. 
     
     
         27 . The method of  claim 25 , wherein the pharmaceutical composition is administered to the subject by applying the composition to a surface of a medical device prior to inserting the medical device into the subject. 
     
     
         28 . (canceled)