Modulators of candida hyphal morphogenesis and uses thereof

Abstract

The invention relates to modulation of fungal morphology between yeast-to-hyphal growth transition by controlling muramyl-L-alanine concentration and uses thereof.

1 - 6 . (canceled) 
     
     
         7 . A method of modulating morphogenesis of a fungus in a patient comprising the steps of:
 (a) preparing a composition comprising an adjuvant and (i) muramyl-L-alanine and/or (ii) a compound having a muramyl-L-alanine in its core structure; and   (b) administering the composition to the patient.   
     
     
         8 . (canceled) 
     
     
         9 . The method of  claim 7 , wherein the compound that includes muramyl-L-alanine in its core structure, includes muramyl-L-alanyl-D-isoglutamine, N-acetyl-muramyl-L-alanine, N-acetylmuramyl-L-alanyl-D-isoglutamine or muramyl-L-alanyl-L-isoglutamine. 
     
     
         10 . The method of  claim 9 , wherein the compound is muramyl-L-alanyl-D-isoglutamine. 
     
     
         11 . The method of  claim 7 , wherein step (b) comprises administering the composition to the patient in series at regular intervals. 
     
     
         12 . The method of  claim 7 , wherein the adjuvant is Freund's complete adjuvant or MPL-TDM (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate) adjuvant. 
     
     
         13 . The method of  claim 7 , wherein the muramyl-L-alanine and/or the compound having a muramyl-L-alanine in its core structure is conjugated to an immunogenic protein. 
     
     
         14 . The method of  claim 13 , wherein the immunogenic protein is a carrier protein. 
     
     
         15 . The method of  claim 13 , wherein the immunogenic protein is unrelated to the muramyl-L-alanine and/or the compound having a muramyl-L-alanine in its core structure. 
     
     
         16 . The method of  claim 15 , wherein the immunogenic protein is keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobulin, soybean trypsin inhibitor or a toxoid. 
     
     
         17 . The method of  claim 16 , wherein the wherein the immunogenic protein is a tetanus toxoid. 
     
     
         18 . The method of  claim 7 , wherein the fungus is  Candida albicans.    
     
     
         19 . A method of modulating morphogenesis of a fungus in a patient comprising the steps of:
 (a) reacting an immunogenic protein with (i) muramyl-L-alanine and/or (ii) a compound having a muramyl-L-alanine in its core structure to form a conjugate;   (b) preparing a composition comprising the conjugate; and   (b) administering the composition to the patient.   
     
     
         20 . The method of  claim 19 , wherein the compound that includes muramyl-L-alanine in its core structure includes muramyl-L-alanyl-D-isoglutamine, N-acetylmuramyl-L-alanine, N-acetylmuramyl-L-alanyl-D-isoglutamine or muramyl-L-alanyl-L-isoglutamine. 
     
     
         21 . The method of  claim 21 , wherein the compound is muramyl-L-alanyl-D-isoglutamine. 
     
     
         22 . The method of  claim 19 , wherein the immunogenic protein is keyhole limpet hemocyanin (KLH), serum albumin, bovine thyroglobulin, soybean trypsin inhibitor or a toxoid. 
     
     
         23 . The method of  claim 22 , wherein the immunogenic protein is tetanus toxoid. 
     
     
         24 . The method of  claim 22 , wherein the immunogenic protein is KLH and is succinylated prior to conjugation. 
     
     
         25 . A composition for stimulating an individual's immune system, the composition comprising muramyl-L-alanine and/or a compound having a muramyl-L-alanine in its core structure. 
     
     
         26 . The composition of  claim 25 , wherein the composition includes an adjuvant. 
     
     
         27 . The composition of  claim 25 , wherein the muramyl-L-alanine and/or the compound having a muramyl-L-alanine in its core structure is conjugated to an immunogenic protein.