Methods of inhibiting Helicobacter pylori

Abstract

A method of treating or preventing Helicobacter infection in humans or animals comprising the step of administering a molecule, such as a molecule that can interact with UreI, capable of inhibiting the growth or survival of Helicobacter in vivo to a human or animal in need of such treatment.

We claim:  
     
         1 . An in vitro method for identifying a molecule capable of inhibiting the growth or survival of Helicobacter in vivo, comprising the steps of: 
 (a) contacting a parental Helicobacter with said molecule in a biological sample;    (b) testing and comparing the response to extracellular pH and the sensitivity to acidity of the parental strain to a strain deficient in UreI and/or of a UreI deficient strain complemented with a plasmid carrying ureI in the presence or absence of said active molecule: and    (c) selecting said molecule displaying a differential effect on the parental strain as compared to the UreI deficient strain.    
     
     
         2 . The method according to  claim 1 , wherein the degree of acidity sensitivity is measured in step (b).  
     
     
         3 . The method according to  claim 1 , wherein the molecules are specific to UreI.  
     
     
         4 . The method according to  claim 1 , wherein the Helicobacter strain is selected from the group consisting of  Helicobacter pylori, helicobacter felis, Helicobacter heilmannii, Helicobacter mustelae, Helicobacter canis, Helicobacter bilis, Helicobacter hepaticus, Helicobacter muridarum , and  Helicobacter troguntum.    
     
     
         5 . A molecule capable of inhibiting the growth or survival of  H. pylori  in vivo identified by the method according to  claim 1 .  
     
     
         6 . A method of treating or preventing  H. pylori  infection in humans or animals comprising the step of administering a molecule according to  claim 5  together with a pharmaceutically acceptable carrier to a human or animal in need of such treatment.  
     
     
         7 . A method of preventing or treating  H. pylori  infection comprising the step of administering a molecule capable of inhibiting the growth or survival of  H. pylori  in vivo to a human or animal in need of such treatment.  
     
     
         8 . The method according to  claim 7 , wherein the molecule is transported inside the  H. pylori  cell due to a high affinity for UreI.  
     
     
         9 . The method according to  claim 7 , wherein the molecule inactivates UreI by inhibiting its properties in  H. pylori  resistance to acidity.  
     
     
         10 . The method according to  claim 7 , wherein the molecule inactivates UreI by inhibiting its properties as a transporter.  
     
     
         11 . The method according to  claim 7 , wherein the molecule inactivates UreI by inhibiting an interaction between UreI and other  H. pylori  proteins.  
     
     
         12 . The method according to  claim 7 , wherein the molecule is capable of intracellular inhibition of urease in  H. pylori.    
     
     
         13 . A molecule capable of inhibiting the growth or survival of  Helicobacter pylori  in vivo said molecule being capable of interacting directly or indirectly with UreI protein or UreI activity or with the corresponding ureI gene.  
     
     
         14 . A molecule according to  claim 13 , wherein the molecule is transported inside the  H. pylori  cell due to a high affinity for ureI.  
     
     
         15 . A molecule according to claims  9  and  13 , wherein the molecule inactivates UreI protein by directly binding to ureI.  
     
     
         16 . A molecule according to claims  10  and  13 , wherein the molecule is specifically inhibiting UreI transporter properties either in ammonia export or in urea transport (export or import).  
     
     
         17 . A molecule according to claims  11  and  13  wherein the molecule is capable of specifically inhibiting an interaction between UreI and other  H. pylori  proteins.  
     
     
         18 . A molecule according to claims  12  and  13  wherein the molecule is capable of intracellular inhibition of  H. pylori  urease.  
     
     
         19 . An immunogenic composition comprising all or part of  H. pylori  UreI and a pharmaceutically acceptable carrier.  
     
     
         20 . A method of preventing  Helicobacter pylori  infection comprising the step of administering an immunogenic composition according to  claim 19 .  
     
     
         21 . Monoclonal or polyclonal antibodies that specifically recognize all or part of  H. pylori  UreI.  
     
     
         22 . A recombinant strain of  H. pylori  comprising a modified ureI gene, wherein the product of the gene contributes to the attenuation of the bacteria's ability to survive in vivo.  
     
     
         23 . A recombinant strain according to  claim 22  named  H. pylori  N6-834 mutant deposited at C.N.C.M. on Jun. 28,1999.  
     
     
         24 . A plasmid pILL 850, deposited at the C.N.C.M. on Jun. 28, 1999 under Accession Number I-2245, able to stably replicate in  H. pylori , carrying the ureI gene and complementing the  H. pylori  N6-834 mutant.