Compositions and methods for treatment of chronic and infectious diseases

Abstract

The present invention generally features therapeutic and diagnostic compositions and methods for increasing or decreasing the binding of a lysozyme polypeptide to a Treponema pallidum P17 polypeptide (Tp17) or a Tp17-like polypeptide. More particularly, the invention relates to compositions and methods for detecting, treating, or preventing a pathogen infection or a chronic disorder; and to binding assays using a Tp17-like polypeptide and a lysozyme polypeptide.

1 - 16 . (canceled)  
     
     
         17 . A substantially pure mutant lysozyme polypeptide comprising at least one amino acid mutation that reduces binding between the mutant lysozyme polypeptide and a Tp17-like polypeptide, wherein the mutant lysozyme polypeptide retains at least 50% of the anti-microbial activity of a corresponding wild-type lysozyme polypeptide.  
     
     
         18 . The polypeptide of  claim 17 , wherein the mutation reduces binding between the mutant lysozyme polypeptide and a Tp17-like polypeptide by at least 5% relative to wild-type lysozyme polypeptide binding.  
     
     
         19 . The polypeptide of  claim 17 , wherein the mutation affects a surface charge in the corresponding wild-type polypeptide.  
     
     
         20 . The polypeptide of  claim 17 , wherein the mutation is in a positively charged, a negatively charged, or a hydrophobic amino acid residue of a wild-type lysozyme polypeptide that contacts a Tp17-like polypeptide.  
     
     
         21 . The polypeptide of  claim 17  comprising a mutation of at least one of amino acid positions selected from the group consisting of Lys19, Arg23, Lys51, Gly 55, Asn57, Arg131, Asn132 and Arg133 of human lysozyme and their corresponding positions in other species.  
     
     
         22 . A substantially pure nucleic acid molecule encoding the lysozyme polypeptide of  claim 17 .  
     
     
         23 . A vector comprising the nucleic acid molecule of  claim 22 .  
     
     
         24 . A host cell comprising the vector of  claim 23 .  
     
     
         25 - 57 . (canceled)  
     
     
         58 . A method for identifying a candidate compound that increases lysozyme anti-microbial activity, the method comprising detecting a reduction in binding between a lysozyme polypeptide and a polypeptide comprising a lysozyme binding motif in the presence of the candidate compound.  
     
     
         59 . The method of  claim 58 , wherein the candidate compound reduces binding of a lysozyme binding motif to a catalytic glutamic acid that corresponds to Glu53 of human lysozyme.  
     
     
         60 . A method for identifying a mutant lysozyme polypeptide having increased anti-microbial activity, the method comprising the steps of: 
 (a) providing a lysozyme polypeptide comprising at least one mutation in the amino acid sequence of the polypeptide relative to a wild-type lysozyme sequence;    (b) detecting a reduction in binding between the mutant lysozyme polypeptide and a Tp17-like polypeptides.    
     
     
         61 . A method for treating or preventing a pathogen infection in a subject in need thereof, the method comprising administering an effective amount of a mutant lysozyme polypeptide comprising an amino acid mutation to a subject, wherein the mutation reduces binding between the lysozyme polypeptide and a Tp17-like polypeptide.  
     
     
         62 . A method for treating or preventing a pathogen infection in a subject in need thereof, the method comprising administering an effective amount of a mutant Tp17-like polypeptide comprising an amino acid mutation to the subject, wherein the administration of the mutant Tp17-like polypeptide reduces the binding between a pathogen-expressed Tp17-like polypeptide and an endogenous lysozyme polypeptide.  
     
     
         63 - 75 . (canceled)  
     
     
         76 . A pharmaceutical composition for use as an anti-microbial comprising at least an effective amount of bacteriophage T4 lysozyme and papain or bacitracin.  
     
     
         77 . The pharmaceutical composition of  claim 76 , wherein the composition comprises bacteriophage T4 lysozyme, papain, and bacitracin.  
     
     
         78 . A method of treating a pathogen infection in a subject comprising administering to a subject diagnosed as having a pathogen infection a pharmaceutical composition comprising bacteriophage T4 lysozyme and papain or bacitracin.  
     
     
         79 - 80 . (canceled)