Novel prokaryotic polynucleotides, polypeptides and their uses

Abstract

The invention provides novel polypeptides and polynucleotides encoding such polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing such polypeptides to screen for antibacterial compounds.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide having at least a 70% identity to a polynucleotide encoding a polypeptide comprising an amino acid sequence of the Sequence Listing;    (b) a polynucleotide having at least a 70% identity to a polynucleotide encoding a mature polypeptide expressed by the gene contained in the  S. aureus  of the deposited strain that was sequenced to obtain a polynucleotide sequence of the Sequence Listing;    (c) a polynucleotide encoding a polypeptide comprising an amino acid sequence which is at least 70% identical to an amino acid sequence of the Sequence Listing;    (d) a polynucleotide which is complementary to the polynucleotide of (a), (b) or (c); and    (e) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a), (b), (c) or (d).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 2  comprising the nucleic acid sequence selected from the group consisting of the nucleic acid sequences set forth in the Sequence Listing.  
     
     
         5 . The polynucleotide of  claim 2  which encodes a polypeptide comprising an amino acid sequence sequence selected from the group consisting of the amino acid sequences set forth in the Sequence Listing.  
     
     
         6 . A vector comprising the polynucleotide of  claim 1 .  
     
     
         7 . A host cell comprising the vector of  claim 6 .  
     
     
         8 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 7  a polypeptide encoded by said DNA.  
     
     
         9 . A process for producing a polypeptide or fragment comprising culturing a host of  claim 7  under conditions sufficient for the production of said polypeptide or fragment.  
     
     
         10 . A polypeptide comprising an amino acid sequence which is at least 70% identical to an amino acid sequence selected from the group consisting of the amino acid sequences set forth in the Sequence Listing.  
     
     
         11 . A polypeptide comprising an amino acid sequence selected from the group consisting of the amino acid sequences set forth in the Sequence Listing.  
     
     
         12 . An antibody against the polypeptide of  claim 10 .  
     
     
         13 . An antagonist or agonist of the activity or expression of the polypeptide of  claim 10 .  
     
     
         14 . A method for the treatment or prevention of disease of an individual comprising: administering to the individual a therapeutically effective amount of the polypeptide of  claim 10 .  
     
     
         15 . A method for the treatment of an individual having need to inhibit a bacterial polypeptide comprising: administering to the individual a therapeutically effective amount of the antagonist of  claim 13 .  
     
     
         16 . A process for diagnosing a disease related to expression or activity of the polypeptide of  claim 10  in an individual comprising: 
 (a) determining a nucleic acid sequence encoding said polypeptide, and/or  
 (b) analyzing for the presence or amount of said polypeptide in a sample derived from the individual.  
 
     
     
         17 . A method for identifying compounds which interact with and inhibit or activate an activity of the polypeptide of  claim 10  comprising: 
 contacting a composition comprising the polypeptide with the compound to be screened under conditions to permit interaction between the compound and the polypeptide to assess the interaction of a compound, such interaction being associated with a second component capable of providing a detectable signal in response to the interaction of the polypeptide with the compound;  
 and determining whether the compound interacts with and activates or inhibits an activity of the polypeptide by detecting the presence or absence of a signal generated from the interaction of the compound with the polypeptide.  
 
     
     
         18 . A method for inducing an immunological response in a mammal which comprises inoculating the mammal with the polypeptide of  claim 10 , or a fragment or variant thereof, adequate to produce antibody and/or T cell immune response to protect said animal from disease.  
     
     
         19 . A method of inducing immunological response in a mammal which comprises delivering a nucleic acid vector to direct expression of a polypeptide of  claim 10 , or fragment or a variant thereof, for expressing said polypeptide, or a fragment or a variant thereof in vivo in order to induce an immunological response to produce antibody and/or T cell immune response to protect said animal from disease.  
     
     
         20 . A polynucleotide comprising a polynucleotide sequence selected from the group consisting of SEQ ID NO: 1, 52, 95, 184, 127, 128, 153, 212, 215 and 227.  
     
     
         21 . A polypeptide comprising a polypeptide encoded by the polynculeotide of  claim 20 .  
     
     
         22 . The isolated polynucleotide of  claim 1  wherein said nucleotide is selected from the group consisting of: 
 (a) a polynucleotide having at least a 90% identity to a polynucleotide encoding a polypeptide comprising the amino acid sequence of the Sequence Listing;  
 (b) a polynucleotide having at least a 90% identity to a polynucleotide encoding the same mature polypeptide expressed by the gene contained in the  S. aureus  of the deposited strain that was sequenced to obtain a polynucleotide sequence of the Sequence Listing;  
 (c) a polynucleotide encoding a polypeptide comprising an amino acid sequence which is at least 90% identical to the amino acid sequence of the Sequence Listing;  
 (d) a polynucleotide which is complementary to the polynucleotide of (a), (b) or (c); and  
 (e) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a), (b), (c) or (d).  
 
     
     
         23 . The isolated polynucleotide of  claim 1  selected from the group consisting of: 
 (a) a polynucleotide having at least a 95% identity to a polynucleotide encoding a polypeptide comprising the amino acid sequence of the Sequence Listing;  
 (b) a polynucleotide having at least a 95% identity to a polynucleotide encoding the same mature polypeptide expressed by the gene contained in the  S. aureus  of the deposited strain that was sequenced to obtain a polynucleotide sequence of the Sequence Listing;  
 (c) a polynucleotide encoding a polypeptide comprising an amino acid sequence which is at least 95% identical to the amino acid sequence of the Sequence Listing;  
 (d) a polynucleotide which is complementary to the polynucleotide of (a), (b) or (c); and  
 (e) a polynucleotide comprising at least 15 sequential bases of the polynucleotide of (a), (b), (c) or (d).  
 
     
     
         24 . An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide having at least a 50% identity to a polynucleotide encoding a polypeptide comprising the amino acid sequence of the Sequence Listing and obtained from a prokaryotic species other than  S. aureus;      (b) a polynucleotide encoding a polypeptide comprising an amino acid sequence which is at least 50% identical to the amino acid sequence of the Sequence Listing and obtained from a prokaryotic species other than  S. aureus;  and    (c) a polynucleotide which is complementary to the polynucleotide of (a) or (b).    
     
     
         25 . An isolated Streptococcal polypeptide having one of the amino acid sequences given in Table 1.  
     
     
         26 . An isolated nucleic acid encoding one of the amino acid sequences of  claim 1  and nucleic acid sequences capable of hybridizing therewith under stringent conditions.  
     
     
         27 . Recombinant vectors comprising the nucleic acid sequences of  claim 26  and host cells transformed or transfected therewith.  
     
     
         28 . A method of identifying an antimicrobial compound comprising contacting candidate compounds with a polypeptide of  claim 1  and selecting those compounds capable of inhibiting the bioactivity of said polypeptide.  
     
     
         29 . Antimicrobial compounds identified by the method of claim  28 .