<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...

Full description

Bibliographic Details
Main Authors: Mamoudou Maiga, Seong Won Choi, Viorel Atudorei, Mariama C. Maiga, Zachary D. Sharp, William R. Bishai, Graham S. Timmins
Format: Article
Language:English
Published: American Society for Microbiology 2014-05-01
Series:mBio
Online Access:https://journals.asm.org/doi/10.1128/mBio.00990-14
_version_ 1818424708837670912
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.
first_indexed 2024-12-14T14:02:21Z
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
work_keys_str_mv AT mamoudoumaiga italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT seongwonchoi italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT viorelatudorei italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT mariamacmaiga italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT zacharydsharp italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT williamrbishai italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase
AT grahamstimmins italictoggleyesinvitroitalicanditalictoggleyesinvivoitalicstudiesofarapidandselectivebreathtestfortuberculosisbaseduponmycobacterialcodehydrogenase