Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test

Seong W. Choi; Mamoudou Maiga; Mariama C. Maiga; Viorel Atudorei; Zachary D. Sharp; William R. Bishai; Graham S. Timmins

doi:10.1038/ncomms5989

Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test

Seong W. Choi, Mamoudou Maiga, Mariama C. Maiga, Viorel Atudorei, Zachary D. Sharp, William R. Bishai, Graham S. Timmins^*

^*Corresponding author for this work

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N 2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of 15 N 2 in exhaled breath of infected rabbits within 5-10â €‰min. No increase in 15 N 2 is detected in uninfected animals, and the increases in 15 N 2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.

Original language	English (US)
Article number	4989
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5989
State	Published - 2014

Funding

This study was funded by NIH Grants AI064386 and AI081015 (G.S.T.) and AI36973 and AI37856 (W.R.B.).

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ncomms5989

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title = "Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test",

abstract = "There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N 2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of 15 N 2 in exhaled breath of infected rabbits within 5-10{\^a} €‰min. No increase in 15 N 2 is detected in uninfected animals, and the increases in 15 N 2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.",

author = "Choi, {Seong W.} and Mamoudou Maiga and Maiga, {Mariama C.} and Viorel Atudorei and Sharp, {Zachary D.} and Bishai, {William R.} and Timmins, {Graham S.}",

note = "Funding Information: This study was funded by NIH Grants AI064386 and AI081015 (G.S.T.) and AI36973 and AI37856 (W.R.B.).",

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AU - Choi, Seong W.

AU - Maiga, Mamoudou

AU - Maiga, Mariama C.

AU - Atudorei, Viorel

AU - Sharp, Zachary D.

AU - Bishai, William R.

AU - Timmins, Graham S.

N1 - Funding Information: This study was funded by NIH Grants AI064386 and AI081015 (G.S.T.) and AI36973 and AI37856 (W.R.B.).

PY - 2014

Y1 - 2014

N2 - There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N 2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of 15 N 2 in exhaled breath of infected rabbits within 5-10â €‰min. No increase in 15 N 2 is detected in uninfected animals, and the increases in 15 N 2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.

AB - There is urgent need for rapid, point-of-care diagnostic tools for tuberculosis (TB) and drug sensitivity. Current methods based on in vitro growth take weeks, while DNA amplification can neither differentiate live from dead organisms nor determine phenotypic drug resistance. Here we show the development and evaluation of a rapid breath test for isoniazid (INH)-sensitive TB based on detection of labelled N 2 gas formed specifically from labelled INH by mycobacterial KatG enzyme. In vitro data show that the assay is specific, dependent on mycobacterial abundance and discriminates between INH-sensitive and INH-resistant (S315T mutant KatG) TB. In vivo, the assay is rapid with maximal detection of 15 N 2 in exhaled breath of infected rabbits within 5-10â €‰min. No increase in 15 N 2 is detected in uninfected animals, and the increases in 15 N 2 are dependent on infection dose. This test may allow rapid detection of INH-sensitive TB.

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Rapid in vivo detection of isoniazid-sensitive Mycobacterium tuberculosis by breath test

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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