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 - 7 . (canceled) 
     
     
         8 . A method for screening for agonists and antagonists of  Candida  hyphal growth comprising steps of:
 (a) contacting with a sample compound (i) muramyl-L-alanine and/or compounds that include muramyl-L-alanine in their core structure and (ii) the leucine-rich-repeat (LRR) domain of CaCdc35p obtained from a  Candida  species; and   (b) detecting whether the sample compound interferes with interaction between muramyl-L-alanine and/or compounds that include muramyl-L-alanine in their core structure and the LRR domain of CaCdc35p of the  Candida  species.   
     
     
         9 . The method of  claim 8 , wherein the sample compound comprises at least one antagonist. 
     
     
         10 . The method of  claim 9 , wherein the antagonist inhibits, removes, degrades, neutralizes or competes with the muramyl-L-alanine and/or compounds that include muramyl-L-alanine in their core structure. 
     
     
         11 . The method of  claim 10 , wherein the antagonist binds to the LRR domain of CaCdc35p of the  Candida  species. 
     
     
         12 . The method of  claim 9 , wherein the compounds that include muramyl-L-alanine in their core structure are selected from the group consisting of: muramyl-L-alanyl-D-isoglutamine, N-acetylmuramyl-L-alanine, N-acetylmuramyl-L-alanyl-D-isoglutamine and muramyl-L-alanyl-L-isoglutamine. 
     
     
         13 . The method of  claim 12 , wherein at least one of the compounds is muramyl-L-alanyl-D-isoglutamine. 
     
     
         14 . The method of  claim 9 , wherein the antagonist is a small molecule. 
     
     
         15 . The method of  claim 14 , wherein the small molecule is selected from the group consisting of: antibodies, antibody fragments, small peptides, peptide-like molecules, and synthetic non-peptidyl organic and inorganic compounds. 
     
     
         16 . The method of  claim 15 , wherein the small molecule is selected from the group consisting of: polyclonal antibodies, monoclonal antibodies, humanized antibodies, bispecific antibodies, heteroconjugate antibodies and mixtures thereof. 
     
     
         17 . The method of  claim 8 , wherein the step of detecting comprises measuring hyphal growth of the  Candida  species. 
     
     
         18 . The method of  claim 8 , wherein the method is, or is part of, a protein binding assay, biochemical screening assay, immunoassay or cell-based assay. 
     
     
         19 . A method for treating a patient infected with  Candida,  the method comprising administering to the patient an antagonist of  Candida  hyphal growth, wherein the antagonist is identified according to the method of  claim 8 . 
     
     
         20 . The method of  claim 19 , wherein the  Candida  is in a body fluid. 
     
     
         21 . The method of  claim 20 , wherein the body fluid is serum. 
     
     
         22 . The method of  claim 19 , wherein the  Candida  species is  Candida albicans.    
     
     
         23 . The method of  claim 19 , wherein the antagonist inhibits, removes, degrades, or neutralizes the hypha-inducing activity of muramyl-L-alanine and/or compounds that include muramyl-L-alanine in their core structure. 
     
     
         24 . A composition comprising:
 an antagonist of  Candida  hyphal growth, wherein the antagonist is identified according to the method of  claim 8 ; and   a pharmaceutically acceptable carrier.   
     
     
         25 . The composition of  claim 24 , wherein the antagonist is capable of inhibiting, removing, degrading or neutralizing the hypha-inducing activity of muramyl-L-alanine and/or compounds that include muramyl-L-alanine in their core structure. 
     
     
         26 . The composition of  claim 25 , wherein the antagonist is an antibody. 
     
     
         27 . The composition of  claim 26 , wherein the antibody is a catalytic antibody.