Antimicrobial fusion peptides

Abstract

Antimicrobial peptides, compositions and methods are described that are useful for treating infectious disease, including those caused by drug resistant Gram-negative bacteria (e.g., Pseudomonas and Acinetobacter ) and parasite-caused disease such as malaria. The peptides include a modular kinocidin gamma-core connected directly, or through a short spacer, to a kinocidin C-terminal alpha-helix.

What is claimed is: 
     
         1 . An isolated peptide comprising:
 (1) a first fragment consisting of the amino acid sequence of SEQ ID NO:2 (CPTAQLIATLKNGRKICLDLQ) or a first amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2; and   (2) a second fragment consisting of the amino acid sequence of SEQ ID NO:3 (ALYKKFKKKLLKSLKRLG) or a second amino acid sequence having at least 85% sequence identity to SEQ ID NO: 3,   wherein the first fragment and the second fragment are connected directly or connected through a spacer that is 10 amino acids or fewer in length, and   wherein the first fragment is at the N-terminal end of the second fragment.   
     
     
         2 . The isolated peptide of  claim 1 , wherein the first fragment and the second fragment are connected directly. 
     
     
         3 . The isolated peptide of  claim 1 , wherein the first fragment and the second fragment are connected through the spacer. 
     
     
         4 . The isolated peptide of  claim 3 , wherein the spacer is 5 amino acids or fewer in length. 
     
     
         5 . The isolated peptide of  claim 1 , comprising the amino acid sequence of SEQ ID NO:1 (CPTAQLIATLKNGRKICLDLQALYKKFKKKLLKSLKRLG). 
     
     
         6 . The isolated peptide of  claim 1 , comprising an amino acid sequence having at least 90% sequence identity to SEQ ID NO:1. 
     
     
         7 . The isolated peptide of  claim 1 , comprising an amino acid sequence having from one to five amino acid substitutions from SEQ ID NO:1. 
     
     
         8 . The isolated peptide of  claim 1 , wherein the peptide is not longer than 100 amino acids in length. 
     
     
         9 . The isolated peptide of  claim 8 , wherein the peptide is not longer than 75 amino acids in length. 
     
     
         10 . The isolated peptide of  claim 8 , wherein the peptide is not longer than 50 amino acids in length. 
     
     
         11 . The isolated peptide of  claim 1 , wherein the peptide has antimicrobial activity. 
     
     
         12 . A polynucleotide comprising a nuclei acid sequence encoding the peptide of  claim 1 . 
     
     
         16 . A composition comprising the peptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         17 . A method of treating an infection in a patient in need thereof, comprising administering to the patient an effective amount of the composition of  claim 16 . 
     
     
         18 . The method of  claim 17 , wherein the infection is caused by multidrug-resistant  Pseudomonas aeruginosa  (MDRPA) or multidrug-resistant  Acinetobacter baumannii  (MDRAB). 
     
     
         19 . The method of  claim 17 , wherein the infection is caused by a parasite. 
     
     
         20 . The method of  claim 19 , wherein the patient suffers from malaria.