US2008014588A1PendingUtilityA1

Compositions and methods for detecting multidrug resistant strains of M. tuberculosis having mutations in genes of the mutT family

67
Assignee: PASTEUR INSTITUTPriority: Aug 14, 2001Filed: May 9, 2007Published: Jan 17, 2008
Est. expiryAug 14, 2021(expired)· nominal 20-yr term from priority
Inventors:Brigitte Gicquel
C12Q 1/689C07K 14/35C12Q 2600/156
67
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Claims

Abstract

The present invention pertains to polynucleotides derived from M. tuberculosis genes imparting resistance to antibiotics and chemically related compounds. This invention also relates to the use of the polynucleotides as oligonucleotide primers or probes for detecting M. tuberculosis strains that are resistant to antibiotics and related compounds in a biological sample. Kits containing the primers and probes are also provided.

Claims

exact text as granted — not AI-modified
1 - 55 . (canceled)  
     
     
         56 . A method for predicting the epidemic character of a  Mycobacterium tuberculosis  isolate and/or a selective advantage to be maintained in a host and/or the acquisition of multiple drug resistance (MDR) by the isolate, wherein the method comprises detecting a mutation in the rpsl locus and a mutation in one or more mutT family member selected from the Rv3908 locus, the mutT2 locus, and the ogt locus of said isolate, wherein the existence of the mutations is indicative of Beijing genotype and MDR phenotype of  Mycobacterium tuberculosis.    
     
     
         57 . The method as claimed in  claim 56  wherein the isolate consists essentially of a Beijing  Mycobacterium tuberculosis  strain.  
     
     
         58 . A method for detecting a  Mycobacterium tuberculosis  strain having a multiple drug resistant (MDR) phenotype, wherein the method comprises detecting a mutation in the rpsl locus and a mutation in the Rv3908 locus of the genome of said  Mycobacterium tuberculosis  strain, wherein the existence of the mutations is indicative of Beijing genotype and MDR phenotype of  Mycobacterium tuberculosis.    
     
     
         59 . The method as claimed in  claim 58 , which comprises detecting a mutation at codon 48 of the Rv3908 locus.  
     
     
         60 . The method as claimed in  claim 59 , which comprises detecting GGG at codon 48.  
     
     
         61 . A method for detecting a  Mycobacterium tuberculosis  strain having a multiple drug resistance (MDR) phenotype, wherein the method comprises detecting a mutation in the rpsl locus and a mutation in the mutT2 locus of the genome of said  Mycobacterium tuberculosis  strain, wherein the existence of the mutations is indicative of Beijing genotype and MDR phenotype of  Mycobacterium tuberculosis.    
     
     
         62 . The method as claimed in  claim 61 , which comprises detecting a mutation at codon 58 of the mutT2 locus.  
     
     
         63 . The method as claimed in  claim 62 , which comprises detecting CGA at codon 58.  
     
     
         64 . A method for detecting a  Mycobacterium tuberculosis  strain having a multiple drug resistance (MDR) phenotype, wherein the method comprises detecting a mutation in the rspl locus and in the ogt locus of the genome of said— Mycobacterium tuberculosis  strain, wherein the existence of the mutations is indicative of Beijing genotype and MDR phenotype of  Mycobacterium tuberculosis.    
     
     
         65 . A method of detecting a  Mycobacterium tuberculosis  strain having a multiple drug resistance (MDR) phenotype, wherein the method comprises: 
 (a) providing a biological sample suspected of containing  Mycobacterium tuberculosis;      (b) amplifying nucleic acids in the sample using as a primer pair 
 (i) SEQ ID NO: 1, and SEQ ID NO: 2; or  
 (ii) SEQ ID NO: 3, and SEQ ID NO: 4; or  
 (iii) SEQ ID NO: 7, and SEQ ID NO: 8; and  
   (c) detecting a mutation in the rpsl locus and a mutation in the Rv3908 locus, or the mutT2 locus, or the ogt locus, of the  Mycobacterium tuberculosis,  wherein the existence of the mutations is indicative of Beijing genotype and MDR phenotype of  Mycobacterium tuberculosis.      
     
     
         66 . The method as claimed in  claim 65 , wherein the isolate consists essentially of a Beijing  Mycobacterium tuberculosis  strain.  
     
     
         67 . The method as claimed in  claim 65 , wherein the isolate contains a mutation in one or more mutT family member selected from the Rv3908 locus, the mutT2 locus, and the ogt locus.  
     
     
         68 . The method as claimed in  claim 65 , wherein step (c) comprises detecting a mutation in the Rv3908 locus of the genome of said  Mycobacterium tuberculosis  strain.  
     
     
         69 . The method as claimed in  claim 68 , which comprises detecting a mutation at codon 48 of the Rv3908 locus.  
     
     
         70 . The method as claimed in  claim 69 , which comprises detecting GGG at codon 48.  
     
     
         71 . The method as claimed in  claim 65 , wherein step (c) comprises detecting a mutation in the mutT2 locus of the genome of said  Mycobacterium tuberculosis  strain.  
     
     
         72 . The method as claimed in  claim 71 , which comprises detecting a mutation at codon 58 of the mutT2 locus.  
     
     
         73 . The method as claimed in  claim 72 , which comprises detecting CGA at codon 58.  
     
     
         74 . The method as claimed in  claim 65 , wherein step (c) comprises detecting a mutation in the ogt locus of the genome of said  Mycobacterium tuberculosis -strain.  
     
     
         75 . A method for detecting whether a patient is infected by a Beijing genotype and MDR phenotype of  M. tuberculosis,  wherein the method comprises assaying a biological specimen from the patient for a mutation in rpsl locus and one or more mutT family members selected from Rv3908 locus, mutT2 locus, and ogt locus of  M. tuberculosis,  wherein the existence of the mutations is indicative of Beijing genotype of and MDR phenotype  Mycobacterium tuberculosis.    
     
     
         76 . A method as claimed in  claim 75 , wherein the method comprises detecting a mutation in the rpsl locus and a mutation in the Rv3908 locus of  Mycobacterium tuberculosis.    
     
     
         77 . The method as claimed in  claim 76 , which comprises detecting a mutation at codon 48 of the Rv3908 locus.  
     
     
         78 . The method as claimed in  claim 77 , which comprises detecting GGG at codon 48.  
     
     
         79 . A method as claimed in  claim 75 , wherein the method comprises detecting a mutation in the mutT2 locus of  Mycobacterium tuberculosis.    
     
     
         80 . The method as claimed in  claim 79 , which comprises detecting a mutation at codon 58 of the mutT2 locus.  
     
     
         81 . The method as claimed in  claim 80 , which comprises detecting CGA at codon 58.  
     
     
         82 . A method as claimed in  claim 75 , wherein the method comprises detecting a mutation in the ogt locus of  Mycobacterium tuberculosis.

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