Nontypeable Haemophilus Influenzae Virulence Factors

Abstract

The invention relates to a mutation within the sap operon of an avirulent clone of a nontypeable strain of Haemophilus influenzae (NTHi). The invention also relates to the NTHi sap operon genes and the polypeptides encoded by these polynucleotide sequences. The invention also relates to a novel 110 kDa NTHi outer membrane protein and the polynucleotide that encodes this outer membrane protein. Methods of screening for NTHi infection, and treating and preventing NTHi related disorders are also contemplated.

1 . An isolated polynucleotide comprising a nucleotide sequence of any one of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 40. 
     
     
         2 . An isolated polynucleotide comprising a nucleotide sequence encoding an amino acid sequence of any one SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or SEQ ID NO: 41. 
     
     
         3 . An isolated polypeptide comprising an amino acid sequence encoded by a nucleotide sequence of  claim 1  or a fragment thereof. 
     
     
         4 . An isolated polypeptide comprising an amino acid sequence of any one SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12 or SEQ ID NO: 41. 
     
     
         5 . A composition comprising a polypeptide of  claim 4  and a pharmaceutically acceptable carrier. 
     
     
         6 . An antibody that specifically binds to a polypeptide of  claim 4  or a fragment thereof. 
     
     
         7 . A composition comprising an antibody of  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         8 . A method for detecting NTHi bacteria in a biological sample comprising
 (a) contacting a polynucleotide of  claim 1  or a fragment thereof with a biological sample, and   (b) detecting hybridization of the polynucleotide within the sample.   
     
     
         9 . A method for detecting NTHi bacteria in a biological sample comprising
 (a) contacting a polynucleotide of  claim 2  or a fragment thereof with a biological sample, and   (b) detecting hybridization of the polynucleotide within the sample.   
     
     
         10 . A method for detecting NTHi bacteria in a biological sample comprising
 (a) contacting an antibody of  claim 6  with a biological sample, and   (b) detecting binding of the antibody within the sample   
     
     
         11 . The method of  claim 8  wherein the biological sample is selected from the group consisting of serum, sputum, ear fluid, blood, urine, lymphatic fluid, and cerebrospinal fluid. 
     
     
         12 . A method for eliciting an immune response to NTHi bacteria comprising administering an immunogenic dose of a polypeptide of  claim 4  or a fragment thereof to a patient at risk of NTHi bacterial infection. 
     
     
         13 . A method of treating or preventing NTHi bacterial infection comprising administering a molecule that inhibits expression or activity of a polypeptide of  claim 4  to an patient in need. 
     
     
         14 . The method of  claim 13  wherein the molecule administered to the patient in need is an antisense oligonucleotide. 
     
     
         15 . The method of  claim 13  wherein the molecule administered to the patient in need is an antibody. 
     
     
         16 . The method of  claim 13  wherein the molecule administered to the patient in need is a small molecule. 
     
     
         17 . The method of  claim 13  wherein the NTHi infection is in the middle ear. 
     
     
         18 - 19 . (canceled)