Chimeric lysm poylpeptides

Abstract

Provided herein are antibacterial compositions and methods of making and using the compositions.

1 . A chimeric polypeptide, said polypeptide decreases the rate of growth of a Gram-negative bacteria, comprising:
 (i) a LysM polypeptide segment exhibiting at least about 70% identity to SEQ ID NO: 2; and   (ii) a heterologous polypeptide sequence exhibiting at least about 10% lower identity to said LysM polypeptide segment.   
     
     
         2 . The chimeric polypeptide of  claim 1 , wherein said decreasing rate of growth is essentially no growth; or said decreasing rate of growth also results in decrease in population of said Gram-negative bacteria. 
     
     
         3 . The chimeric polypeptide of  claim 1 , wherein said heterologous polypeptide comprises sequence derived from a polypeptide from a different organism from said LysM polypeptide. 
     
     
         4 . The chimeric polypeptide of  claim 1 , wherein said Gram-negative bacteria is from a genus selected from  Klebsiella, Acinetobacter, Pseudomonas , or  Escherichia.    
     
     
         5 . The chimeric polypeptide of  claim 1 , wherein said at least about 70% identity to SEQ ID NO: 2 is at least about 80%, and said heterologous polypeptide sequence exhibiting less than about 70% identity to said LysM polypeptide segment. 
     
     
         6 . The chimeric polypeptide of  claim 1 , wherein said at least about 70% identity to SEQ ID NO:2 is at least about 90%, and said heterologous polypeptide sequence exhibiting less than about 80% identity to said LysM polypeptide segment. 
     
     
         7 . The chimeric polypeptide of  claim 1 , wherein said heterologous polypeptide sequence is derived from: (a) a phage endolysin; (b) a phage structure associated muralytic enzyme (ectolysin); (c) a lipopolysachharide binding protein (LBP); (d) an AntiMicrobial Peptide (AMP); or (e) a bactericidal permeability increasing protein (BPI). 
     
     
         8 . The chimeric polypeptide of  claim 1 , wherein said heterologous polypeptide sequence comprises 6xHis or a segment from GP36CD, phi29 endolysin, BPI TMD, LBP, WLBU2, phiKZ, GP144, GP181 lysozyme, phi6 P5, BP7 lysozyme, or SUSHI peptide. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . A nucleic acid encoding the chimeric polypeptide of  claim 1   
     
     
         13 . A cell comprising the nucleic acid of  claim 12 . 
     
     
         14 - 15 . (canceled) 
     
     
         16 . A chimeric polypeptide, said polypeptide accesses the periplasmic space of a Gram-negative bacterium from outside of the cell, comprising:
 (i) a LysM polypeptide segment exhibiting at least about 70% identity to SEQ ID NO: 2; and   (ii) a heterologous polypeptide sequence exhibiting at least about 10% lower identity to said LysM polypeptide segment.   
     
     
         17 . The chimeric polypeptide of  claim 16 , wherein at least some portion of said polypeptide accesses the periplasmic space of said Gram-negative bacteria; said access of said polypeptide results in a decrease in rate of growth of said bacteria; or said decrease in rate of growth of said bacteria results in decrease in population of said Gram-negative bacteria. 
     
     
         18 . The chimeric polypeptide of  claim 16 , wherein said heterologous polypeptide comprises sequence derived from a polypeptide from a different organism from said LysM polypeptide. 
     
     
         19 . The chimeric polypeptide of  claim 16 , wherein said Gram-negative bacteria is from a genus selected from  Klebsiella, Acinetobacter, Pseudomonas , or  Escherichia.    
     
     
         20 . The chimeric polypeptide of  claim 16 , wherein said at least about 70% identity to SEQ ID NO: 2 is at least about 80%, and said heterologous sequence exhibits less than about 70% identity to said LysM polypeptide segment. 
     
     
         21 . The chimeric polypeptide of  claim 16 , wherein said at least about 70% identity to SEQ ID NO: 2 is at least about 90%, and said heterologous sequence exhibits less than about 80% identity to said LysM polypeptide segment. 
     
     
         22 . The chimeric polypeptide of  claim 16 , wherein said heterologous polypeptide sequence is derived from: (a) a phage endolysin; (b) a phage structure associated muralytic enzyme (ectolysin); (c) a lipopolysachharide binding protein (LBP); (d) an AntiMicrobial Peptide (AMP); or (e) a bactericidal permeability increasing protein (BPI). 
     
     
         23 . The chimeric polypeptide of  claim 16 , wherein said heterologous polypeptide sequence comprises 6xHis or a segment from GP36CD, phi29 endolysin, BPI TMD, LBP, WLBU2, phiKZ, GP144, GP181 lysozyme, phi6 P5, BP7 lysozyme, or SUSHI peptide. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . A nucleic acid encoding the chimeric polypeptide of  claim 16 . 
     
     
         28 . A cell comprising the nucleic acid of  claim 27 . 
     
     
         29 - 30 . (canceled)