Reducing conjugative plasmids in bacteria

Abstract

The present invention provides methods and compositions to reduce prevalence of plasmids in microbial colonies, including infections, and includes therapeutic compositions, methods for treatment of infections, and methods for identifying additional such compositions. Means are provided to reduce the copy numbers of antibiotic resistance genes, and to confer phage binding to cells lacking receptors for those phage.

What is claimed is: 
     
         1 . A genetic construct comprising a segment encoding a phage receptor component driven by a strong heterologous promoter functional in a target bacterium which can serve as host to a lytic phage using said receptor. 
     
     
         2 . The genetic construct of  claim 1 , wherein said:
 a) strong promoter induces high expression of said component which increases binding by at least 5-fold of phage to said host;   b) promoter is an inducible promoter;   c) construct further comprises a selectable marker closely linked to said receptor component;   d) target bacterium is a Gram-negative bacterium; or   e) construct can transfect bacteria in an infection.   
     
     
         3 . A pharmaceutical composition comprising a transmissible DNA encoding a phage receptor which binds to a lytic phage, wherein said lytic phage will kill a bacterial cell expressing said phage receptor, and a pharmaceutically acceptable excipient. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein said:
 a) transmissible DNA is an Inc plasmid selected from N, P, W, D, M, X, P1, U, W, C, or J; or   b) said lytic phage is a phage designated PRD1, PRR1, PR3, PR4, PRS, L17, PR772, GIL01, pGIL01, BAM35, or GIL16.   
     
     
         5 . A kit comprising one or more compartments with said lytic phage of  claim 3  and said pharmaceutical composition.