Live-attenuated compositions for bacterial infections

Abstract

The present invention relates to compositions and methods for disease treatment and prevention through administration of a live attenuated composition. In particular, the present invention provides compositions and methods for the treatment and prevention of urinary tract infection by administration of a live attenuated compositions lacking O-antigen ligase activity.

We claim: 
     
         1 . A method of treating bacterial infection in a subject comprising administering to said subject a live attenuated composition lacking or reduced in O-antigen ligase function. 
     
     
         2 . The method of  claim 1 , wherein said subject is experiencing a urinary tract infection. 
     
     
         3 . The method of  claim 1 , wherein said subject is at risk of experiencing a urinary tract infection. 
     
     
         4 . The method of  claim 1 , wherein the subject is human. 
     
     
         5 . The method of  claim 1 , wherein said lack or reduction in O-antigen ligase function is promoted by altering characteristics selected from the group consisting of O-antigen ligase activity, O-antigen ligase protein level, O-antigen ligase protein stability, O-antigen ligase transcript, and O-antigen ligase transcript stability. 
     
     
         6 . The method of  claim 1 , wherein said lack of reduction in O-antigen ligase function is the result of mutation or deletion of an O-antigen ligase-encoding gene. 
     
     
         7 . The method of  claim 6 , wherein said O-antigen ligase-encoding gene is waaL. 
     
     
         8 . The method of  claim 1 , wherein said live attenuated composition comprises a strain of  E. coli.    
     
     
         9 . The method of  claim 8 , wherein said strain of  E. coli  is uropathogenic. 
     
     
         10 . The method of  claim 1 , wherein said live attenuated composition is NU14 ΔwaaL. 
     
     
         11 . A composition comprising a live attenuated bacterial strain lacking or reduced in O-antigen ligase function. 
     
     
         12 . The composition of  claim 11 , wherein said lack or reduction in O-antigen ligase function is promoted by altering characteristics selected from among the group consisting of O-antigen ligase activity, O-antigen ligase protein level, O-antigen ligase protein stability, O-antigen ligase transcript, and O-antigen ligase transcript stability 
     
     
         13 . The composition of  claim 11 , wherein said lack or reduction in O-antigen ligase function is the result of mutation or deletion of an O-antigen ligase-encoding gene. 
     
     
         14 . The composition of  claim 13 , wherein said O-antigen ligase-encoding gene is waaL. 
     
     
         15 . The composition of  claim 11 , wherein said bacterial strain is a strain of  E. coli.    
     
     
         16 . The composition of  claim 15 , wherein said  E. coli  strain is uropathogenic. 
     
     
         17 . The composition of  claim 11 , wherein said bacterial strain is NU14 ΔwaaL. 
     
     
         18 . The composition of  claim 11 , further comprising an adjuvant. 
     
     
         19 . The composition of  claim 11 , wherein said live attenuated bacterial strain lacking or reduced in O-antigen ligase function is formulated for therapeutic administration to a subject.