Phage derived antimicrobial activities

Abstract

The present invention provides methods and compositions to reduce growth of microbial colonies, including infections, and includes therapeutic compositions, methods for treatment of infections, and methods for identifying additional such compositions.

1 - 44 . (canceled) 
     
     
         45 . A nucleic acid comprising a polynucleotide sequence encoding a chimeric polypeptide that comprises:
 (i) a first sequence having at least 90% identity to the sequence of amino acids 669-808 of SEQ ID NO:1, and   (ii) a heterologous cell binding domain (CBD) that binds to a target bacterium,   wherein the CBD has a sequence with at least 90% identity to a sequence selected from the group consisting of:   amino acids 144-240 of SEQ ID NO:4;   amino acids 149-257 of SEQ ID NO:8; and   amino acids 144-243 of SEQ ID NO:12,   and wherein the target bacterium exhibits reduced or no growth after being contacted with the chimeric polypeptide.   
     
     
         46 . The nucleic acid of  claim 45 , which is an expression cassette driving the expression of the chimeric polypeptide. 
     
     
         47 . The nucleic acid of  claim 45 , wherein the CBD comprises a sequence with at least 90% identity to amino acids 144-240 of SEQ ID NO:4. 
     
     
         48 . The nucleic acid of  claim 47 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO:1 and the CBD comprises the sequence of amino acids 144-240 of SEQ ID NO:4. 
     
     
         49 . The nucleic acid of  claim 47 , wherein the CBD comprises a sequence with at least 90% identity to amino acids 149-257 of SEQ ID NO:8. 
     
     
         50 . The nucleic acid of  claim 49 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO:1 and the CBD comprises the sequence of amino acids 149-257 of SEQ ID NO:8. 
     
     
         51 . The nucleic acid of  claim 48 , wherein the CBD comprises a sequence with at least 90% identity to amino acids 144-243 of SEQ ID NO:12. 
     
     
         52 . The nucleic acid of  claim 51 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO:1 and the CBD comprises the sequence of amino acids 144-243 of SEQ ID NO:12. 
     
     
         53 . The nucleic acid of  claim 49 , wherein the first sequence is a muralytic domain (MD). 
     
     
         54 . The nucleic acid of  claim 50 , wherein the first sequence has at least 90% identity to the sequence of amino acids 629-808 of SEQ ID NO:1. 
     
     
         55 . A nucleic acid comprising a polynucleotide sequence encoding a chimeric polypeptide comprising
 (i) first sequence having at least 90% identity to the sequence of amino acids 669-808 of SEQ ID NO:1, and   (ii) a second sequence having at least 90% identity to a sequence selected from the group consisting of:   (a) amino acids 144-240 of SEQ ID NO:4,   (b) amino acids 149-257 of SEQ ID NO:8, and   (c) amino acids 144-243 of SEQ ID NO:12,   wherein contact with the chimeric polypeptide reduces growth of a target bacterium.   
     
     
         56 . The nucleic acid of  claim 55 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO: 1 and the second sequence comprises the sequence of amino acids 144-240 of SEQ ID NO:4. 
     
     
         57 . The nucleic acid of  claim 56 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO: 1 and the second sequence comprises the sequence of amino acids 149-257 of SEQ ID NO:8. 
     
     
         58 . The nucleic acid of  claim 57 , wherein the first sequence comprises the sequence of amino acids 669-808 of SEQ ID NO: 1 and the CBD comprises the sequence of amino acids 144-243 of SEQ ID NO:12. 
     
     
         59 . The nucleic acid of  claim 58 , wherein the first sequence has at least 90% identity to the sequence of amino acids 629-808 of SEQ ID NO:1. 
     
     
         60 . A method for treating a bacterial infection comprising administering to a subject in need thereof the chimeric polypeptide of  claim 45 . 
     
     
         61 . A method for degrading a bacterial cell wall comprising contacting the bacterial cell wall with a chimeric polypeptide encoded by the nucleic acid of  claim 45 . 
     
     
         62 . A method for disinfecting a surface, comprising contacting the surface with a chimeric polypeptide encoded by the nucleic acid of  claim 45 . 
     
     
         63 . A method for treating a bacterial infection comprising administering to a subject in need thereof a chimeric polypeptide encoded by the nucleic acid of  claim 55 . 
     
     
         64 . A method for degrading a bacterial cell wall comprising contacting the bacterial cell wall with a chimeric polypeptide encoded by the nucleic acid of  claim 55 . 
     
     
         65 . A method for disinfecting a surface, comprising contacting the surface with a chimeric polypeptide encoded by the nucleic acid of  claim 55 .