<italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase
ABSTRACT One of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of...
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Format: | Article |
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American Society for Microbiology
2014-05-01
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Series: | mBio |
Online Access: | https://journals.asm.org/doi/10.1128/mBio.00990-14 |
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author | Mamoudou Maiga Seong Won Choi Viorel Atudorei Mariama C. Maiga Zachary D. Sharp William R. Bishai Graham S. Timmins |
author_facet | Mamoudou Maiga Seong Won Choi Viorel Atudorei Mariama C. Maiga Zachary D. Sharp William R. Bishai Graham S. Timmins |
author_sort | Mamoudou Maiga |
collection | DOAJ |
description | ABSTRACT One of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism’s CO dehydrogenase activity. After development of the test in vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host. IMPORTANCE Tuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2. |
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format | Article |
id | doaj.art-851a2229eb62494c94bb4c36f2be6d40 |
institution | Directory Open Access Journal |
issn | 2150-7511 |
language | English |
last_indexed | 2024-12-14T14:02:21Z |
publishDate | 2014-05-01 |
publisher | American Society for Microbiology |
record_format | Article |
series | mBio |
spelling | doaj.art-851a2229eb62494c94bb4c36f2be6d402022-12-21T22:58:42ZengAmerican Society for MicrobiologymBio2150-75112014-05-015210.1128/mBio.00990-14<italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO DehydrogenaseMamoudou Maiga0Seong Won Choi1Viorel Atudorei2Mariama C. Maiga3Zachary D. Sharp4William R. Bishai5Graham S. Timmins6Department of Medicine, Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USADepartment Earth and Planetary Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USADepartment of Medicine, Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USADepartment Earth and Planetary Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USADepartment of Medicine, Center for Tuberculosis Research, Johns Hopkins University, Baltimore, Maryland, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico, USAABSTRACT One of the major hurdles in treating tuberculosis (TB) is the time-consuming and difficult methodology for diagnosis. Stable-isotope breath tests hold great potential for rapidly diagnosing an infectious disease, monitoring therapy, and determining a bacterial phenotype in a rapid, point-of-care manner that does not require invasive sampling. Here we describe the preclinical development of a potentially highly selective TB diagnostic breath test based upon the organism’s CO dehydrogenase activity. After development of the test in vitro, we were able to use the breath test to discriminate between infected and control rabbits, demonstrating that a diagnosis can potentially be made and also that a complex bacterial phenotype can be noninvasively and rapidly studied in the host. IMPORTANCE Tuberculosis (TB) remains a major infectious cause of disease and death worldwide, and effective diagnosis and then treatment are the tools with which we fight TB. The more quickly and more specific the diagnosis can be made, the better, and this is also true of diagnosis being as close to the patient (point of care) as possible. Here we report our preclinical development of breath tests based upon specific mycobacterial metabolism that could, with development, allow rapid point-of-care diagnosis through measuring the mycobacterial conversion of labeled CO to labeled CO2.https://journals.asm.org/doi/10.1128/mBio.00990-14 |
spellingShingle | Mamoudou Maiga Seong Won Choi Viorel Atudorei Mariama C. Maiga Zachary D. Sharp William R. Bishai Graham S. Timmins <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase mBio |
title | <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase |
title_full | <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase |
title_fullStr | <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase |
title_full_unstemmed | <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase |
title_short | <italic toggle="yes">In Vitro</italic> and <italic toggle="yes">In Vivo</italic> Studies of a Rapid and Selective Breath Test for Tuberculosis Based upon Mycobacterial CO Dehydrogenase |
title_sort | italic toggle yes in vitro italic and italic toggle yes in vivo italic studies of a rapid and selective breath test for tuberculosis based upon mycobacterial co dehydrogenase |
url | https://journals.asm.org/doi/10.1128/mBio.00990-14 |
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