Antibody-mediated disruption of quorum sensing in bacteria
The invention provides an immunogenic molecular entity, a supramolecular assembly, and an antibody 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.
1. An immunogenic molecular entity comprising at least one hapten covalently 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 of YST(X a+2 )DFIM (SEQ ID: 92); wherein the last amino acid residue 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; 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 2 , wherein the macromolecular carrier comprises a protein.
4. The immunogenic molecular entity of claim 1 , wherein the cyclic peptide is covalently linked to the macromolecular carrier.
5. An immunogenic molecular entity having the structure:
SEQ ID NO: 3 (YSTSDFIM, not including protecting groups),
wherein CPL, is a macromolecular carrier with linker covalently bonded to a cysteine thiol group.
6. A vaccine composition comprising at least one immunogenic molecular entity of claim 1 and a pharmaceutically-acceptable carrier.
7. A method of eliciting an immune response in a mammal comprising administering to the mammal a composition comprising the immunogenic molecular entity of claim 1 , in an amount effective to elicit an immune response in the mammal; wherein the mammal is susceptible to infection by Staphylococcus aureus.
8. A method of inhibiting quorum sensing in a mammal comprising administering to the mammal the immunogenic molecular entity of claim 1 , in an amount effective to elicit an immune response and inhibit the quorum sensing in the mammal.
9. A method for 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 treat infection of the mammal by Staphylococcus aureus.