US2012157522A1PendingUtilityA1

B. Anthracis Prevention and Treatment: Mutant B. Anthracis Lacking Luxs Activity and Furanone Inhibition of Growth, AI-2 Quorum Sensing, and Toxin Production

47
Individually held — no corporate assignee on recordPriority: Apr 11, 2003Filed: Apr 21, 2011Published: Jun 21, 2012
Est. expiryApr 11, 2023(expired)· nominal 20-yr term from priority
Inventors:Marcus B. JonesMartin J. BlaserThomas WoodDacheng Ren
A61P 31/04C07K 14/32
47
PatentIndex Score
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Cited by
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References
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Claims

Abstract

The present invention pertains to the discovery that B. anthracis possesses a luxS gene that encodes a functional LuxS polypeptide, and that B. anthracis synthesizes a functional AI-2 quorum-sensing molecule. The invention provides mutant B. anthracis bacteria lacking the function of the luxS gene, which do not produce a functional AI-2 molecule and have growth defects compared to wild-type B. anthracis . The invention also concerns methods for inhibiting the growth of B. anthracis , or for preventing or treating B. anthracis infection, by inhibiting the activity of the B. anthracis LuxS polypeptide, or by exposure of the B. anthracis to furanone. In particular, the invention concerns the use of furanone, a compound that inhibits AI-2-mediated quorum-sensing, to inhibit the growth of B. anthracis , to inhibit B. anthracis toxin production, particularly that of protective antigen, and to prevent or treat B. anthracis infection. The invention also provides methods to prevent B. anthracis infection, or enhance an immune response to B. anthracis infection, by administering a vaccine comprising a B. anthracis cell in which the luxS gene is mutated.

Claims

exact text as granted — not AI-modified
1 - 44 . (canceled) 
     
     
         45 . A method for the treatment or prevention of  B. anthracis  infection in a subject in need of such prevention or treatment, which comprises administering to the subject a therapeutically effective amount of a furanone selected from the group consisting of (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, 3-butyl-5-(dibromomethylene)-2-(5H)-furanone, 5-(bromomethylene)-2-(5H)-furanone, 4-bromo-5-(bromomethylene)-2(5H)-furanone, and 5-(dibromomethylene)-2(5H)-furanone. 
     
     
         46 . The method of  claim 45 , wherein the subject is a human. 
     
     
         47 . The method of  claim 45 , wherein the furanone is (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone. 
     
     
         48 . The method of  claim 45 , wherein the furanone is inhibiting the  B. anthracis  AI-2 quorum-sensing molecule. 
     
     
         49 - 51 . (canceled) 
     
     
         52 . A method for the treatment or prevention of  B. anthracis  infection in a subject in need of such prevention or treatment, which method comprises administering a therapeutically effective amount of an inhibitor of the  B. anthracis  protective antigen. 
     
     
         53 . The method of  claim 52 , wherein the inhibition comprises inhibiting protective antigen gene expression. 
     
     
         54 . The method of  claim 52 , wherein the inhibition comprises inhibiting protective antigen protein expression or activity. 
     
     
         55 . The method of  claim 52 , wherein the inhibitor of the  B. anthracis  protective antigen is a furanone selected from the group consisting of (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, 3-butyl-5-(dibromomethylene)-2-(5H)-furanone, 5-(bromomethylene)-2-(5H)-furanone, 4-bromo-5-(bromomethylene)-2(5H)-furanone, and 5-(dibromomethylene)-2(5H)-furanone. 
     
     
         56 . The method of  claim 55 , wherein the furanone is (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone. 
     
     
         57 - 64 . (canceled) 
     
     
         65 . A method of treating a  B. anthracis  infection in a human in need of such treatment which comprises administering to said human an effective amount for treating such infection of a pharmaceutical composition comprising an inhibitor of  B. anthracis  growth and a pharmaceutically acceptable carrier, wherein the inhibitor of  B. anthracis  growth is a furanone selected from the group consisting of (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)— furanone, 3-butyl-5-(dibromomethylene)-2-(5H)-furanone, 5-(bromomethylene)-2-(5H)-furanone, 4-bromo-5-(bromomethylene)-2(5H)-furanone, and 5-(dibromomethylene)-2(5H)-furanone. 
     
     
         66 . The method of  claim 65 , wherein the composition is administered in a range from about 10 to 50 mg/kg. 
     
     
         67 - 69 . (canceled)

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