Antibody-mediated disruption of quorum sensing in bacteria

Abstract

The invention provides an immunogenic molecular entity and related vaccines that can be used to inhibit Gram-positive bacterial quorum sensing, prevent infection or development of a disease condition associated with a Gram-positive bacterial infection. The invention also provides methods of inhibiting Gram-positive bacterial quorum sensing, and methods of preventing infection or development of a disease condition associated with a Gram-positive bacterial infection.

What is claimed is: 
     
         1 . An immunogenic molecular entity comprising at least one hapten linked to a macromolecular carrier, wherein the hapten comprises a cyclic peptide comprising a macrocyclic ring, wherein the cyclic peptide comprises the amino acid sequence selected from the group consisting of GVNP(X a+2 )GGWF (SEQ ID NO: 96), KAKT(X a+2 )TVLY (SEQ ID NO: 97), KTKT(X a+2 )TVLY (SEQ ID NO: 98), GANP(X a+2 )OLYY (SEQ ID NO: 99), GANP(X a+2 )ALYY (SEQ ID NO: 100), GYST(X a+2 )SYYF (SEQ ID NO: 101), GYRT(X a+2 )NTYF (SEQ ID NO: 102), YNP(X a+2 )VGYF (SEQ ID NO: 103), GGKV(X a+2 )SAYF (SEQ ID NO: 104), SVKP(X a+2 )TGFA (SEQ ID NO: 105), DSV(X a+2 )ASYF (SEQ ID NO: 106), KYNP(X a+2 )SNYL (SEQ ID NO: 107), KYNP(X a+2 )ASYL (SEQ ID NO: 108), KYNP(X a+2 )ANYL (SEQ ID NO: 109), RIPT(X a+2 )TGFF (SEQ ID NO: 110), DI(X a+2 )NAYF (SEQ ID NO: 111), DM(X a+2 )NGYF (SEQ ID NO: 112), KYNP(X a+2 )LGFL (SEQ ID NO: 113), KYYP(X a+2 )FGYF (SEQ ID NO: 114), GARP(X a+2 )GGFF (SEQ ID NO: 115), GAKP(X a+2 )GGFF (SEQ ID NO: 116), YSP(X a+2 )TNFF (SEQ ID NO: 117), YSP(X a+2 )TNF (SEQ ID NO: 118), or QN(X a+2 )PNIFGQWM (SEQ ID NO: 119),
 wherein the last amino acid residue of each sequence is X 1  which is an amino acid residue that is covalently bonded to a group R by a respective carbonyl group;   X a+2  is any amino acid, a respective carbon atom of which is covalently bonded to R;   wherein R comprises —CH 2 O—, —CH 2 CH 2 O—, —CH 2 CH(CH 3 )O—, —CH 2 -phenyl-O—, —CH 2 S—, —CH 2 CH 2 S—, or —(CH 2 ) n NH—, wherein n is 1 to about 4; and   wherein the N-terminal amino acid residue of the cyclic peptide is attached to the macromolecular carrier.   
     
     
         2 . The immunogenic molecular entity of  claim 1 , wherein the macromolecular carrier comprises a protein, a polymer or a nanoparticle. 
     
     
         3 . The immunogenic molecular entity of  claim 1 , wherein the cyclic peptide or analog thereof is covalently linked to the macromolecular carrier. 
     
     
         4 . A method for preventing or treating infection of a mammal by  Staphylococcus aureus  comprising administering to the mammal, the immunogenic molecular entity of  claim 1 , in an amount effective to prevent or treat infection of the mammal by  Staphylococcus aureus.    
     
     
         5 . A method for preventing or treating infection of a mammal by  Staphylococcus intermedius  comprising administering to the mammal, the immunogenic molecular entity comprising macrocyclic ring, wherein the cyclic peptide comprises the amino acid sequence RIPT(X a+2 )TGFF (SEQ ID NO: 110), wherein the last amino acid residue of each sequence is X 1  which is an amino acid residue that is covalently bonded to a group R by a respective carbonyl group;
 X a+2  is any amino acid, a respective carbon atom of which is covalently bonded to R;   wherein R comprises —CH 2 O—, —CH 2 CH 2 O—, —CH 2 CH(CH 3 )O—, —CH 2 -phenyl-O—, —CH 2 S—, —CH 2 CH 2 S—, or —(CH 2 ) n NH—, wherein n is 1 to about 4; and   wherein the N-terminal amino acid residue of the cyclic peptide is attached to the macromolecular carrier, in an amount effective to prevent or treat infection of the mammal by  Staphylococcus intermedius.