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Method of Diagnosing Multidrug Resistant Tuberculosis

20:00 EDT 31 Aug 2000 | NIH

The invention can be used to develop tests that are much more rapid than conventional tests for determining drug resistance. It relates to the discovery that a putative gene of Mycobacterium tuberculosis (MTb) with no previously identified function is responsible for the ability of the bacteria to activate a class of second line thioamide drugs used for MTb infections. The gene, termed "etaA", codes for the synthesis of a monooxygenase, the enzyme responsible for the oxidative activation of the drugs. Mutation in the etaA gene leads to the expression of mutated, inactivated enzyme, thus resulting in thioamide drug-resistant bacteria. The significance of this discovery is that now, resistance to the class of thioamide drugs in clinical isolates can be identified in a relatively short time, eliminating the need to perform lengthy culturing procedures.

The invention claims test methods for determining resistance to thioamide drugs by detecting gene mutation. These include (a) amplifying the etaA gene or a portion of it containing the mutation, with a set of primers which provide amplified product, and sequencing the amplified product to compare the sequence with a known sequence of the wild-type etaA; a difference in sequence patterns indicates mutation; (b) subjecting the amplified gene product to digestion by restriction enzymes and comparing the cleaved DNA gel pattern to the one obtained from digestion of the wild type etaA gene; a difference indicates mutation in etaA; and (c) detecting the mutations by probe hybridization techniques, where the amplified product hybridizes to a nucleic acid of known sequence under stringent conditions, and the hybridized product is detected. In addition to the above, the invention proposes other detection methods such as commonly used for SNPs. Other methods claimed in the invention are immunoassay (i.e., ELISA) for the etaA gene product or mutated versions of it, or immunoassay and chemical analysis of the drug metabolites, whereby the absence of the metabolites indicates gene mutation and impaired activating ability.

IC: 
NIAID
NIH Ref. No.: 
E-093-2000-0
TAB No: 
TAB-1115
Advantages: 
  • Novel methods for diagnosing multidrug resistant tuberculosis that are much more rapid than conventional tests.
Applications: 
  • Infectious diseases, diagnostics (bacterial)
  • Infectious diseases, therapeutics (anti-bacterial)
Provider Technology ID: 
1115
Updated On: 
May 1, 2018
Date Published: 
Friday, September 1, 2000
Provider Classifications: 
Patent Application: 
11/058,484
09/888,320
60/214,187
Publications: 
Patent Authority: 
US
US
US
Patent Number: 
7,547,519
6,905,822
Licensing Contacts: 
Lead Inventor: 
Inventor IC: 
NIAID
NIAID
Inventor Lab URL: 
https://irp.nih.gov/pi/clifton-barry
LPM FIrst Name: 
Po-Lung (David)
LPM Last Name: 
Yang
LPM Address: 
BG 5601FL RM 6D28 MSC 9804 5601 FISHERS LN
LPM City: 
Bethesda
LPM Zip: 
20892-9804
Inv Is lead: 
LPM State: 
MD
LPM Phone: 
301-496-2644
LPM Suffix: 
Ph.D.
LPM Organization: 
NIH Office of Technology Transfer
DTDT Classification: 
Infectious Diseases
Diagnostics
Bacterial
Therapeutics
Anti-bacterial
Disease Initiatives, Rare Disease
DTDT Description: 
Infectious Diseases
Infectious Diseases - Diagnostics
Infectious Diseases - Diagnostics: Bacterial
Infectious Diseases - Therapeutics
Infectious Diseases - Therapeutics: Anti-bacterial
Disease Initiatives, Rare Disease
Pat Filing Date: 
2005-02-14
2001-06-22
2000-06-26
Patent Issue Date: 
2009-06-16
2005-06-14
Publication Link: 
https://www.ncbi.nlm.nih.gov/pubmed/10944230
Publication Caption: 
PMID 10944230
Publication Title: 

DeBarber AE, et al.

Disease Area Term: 
Collaboration Sought: 
Yes
Institute or Center: 
E Number Only: 
E-093-2000-0
Inventor First Name: 
Clifton
Khisimuzi
Inventor Last Name: 
Barry
Mdluli

Original Article: Method of Diagnosing Multidrug Resistant Tuberculosis

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