Cargando…

Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy

Preclinical efforts to discover and develop new drugs and vaccines for tuberculosis are hampered by the reliance on colony-forming unit (CFU) counts as primary outcomes for in vivo efficacy studies and the slow growth of Mycobacterium tuberculosis. The utility of bioluminescent M. tuberculosis repor...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Tianyu, Li, Si-Yang, Nuermberger, Eric L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256174/
https://www.ncbi.nlm.nih.gov/pubmed/22253776
http://dx.doi.org/10.1371/journal.pone.0029774
_version_ 1782221047779557376
author Zhang, Tianyu
Li, Si-Yang
Nuermberger, Eric L.
author_facet Zhang, Tianyu
Li, Si-Yang
Nuermberger, Eric L.
author_sort Zhang, Tianyu
collection PubMed
description Preclinical efforts to discover and develop new drugs and vaccines for tuberculosis are hampered by the reliance on colony-forming unit (CFU) counts as primary outcomes for in vivo efficacy studies and the slow growth of Mycobacterium tuberculosis. The utility of bioluminescent M. tuberculosis reporter strains for real-time in vitro and ex vivo assessment of drug and vaccine activity has been demonstrated but a simple, non-invasive, real-time surrogate marker to replace CFU counts for real-time evaluation of drug and vaccine efficacy in vivo has not been described. We describe the development of a fully virulent and stable autoluminescent strain of M. tuberculosis and proof-of-concept experiments demonstrating its utility for in vivo bioluminescence imaging to assess the efficacy of new drugs and vaccines for tuberculosis in a mouse model. Relative light unit (RLU) counts paralleled CFU counts during the active phase of bacterial growth, with a lower limit of detection of approximately 10(6) CFU in live, anesthetized mice. Experiments distinguishing active from inactive anti-tuberculosis drugs and bacteriostatic drug effects from bactericidal effects were completed in less than 5 days. The ability of a recombinant BCG vaccine to limit bacterial growth was demonstrated within 3 weeks. Use of this autoluminescent reporter strain has the potential to drastically reduce the time, effort, animals and costs consumed in the evaluation of drug activity in vitro and the in vivo assessment of drug and vaccine efficacy.
format Online
Article
Text
id pubmed-3256174
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-32561742012-01-17 Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy Zhang, Tianyu Li, Si-Yang Nuermberger, Eric L. PLoS One Research Article Preclinical efforts to discover and develop new drugs and vaccines for tuberculosis are hampered by the reliance on colony-forming unit (CFU) counts as primary outcomes for in vivo efficacy studies and the slow growth of Mycobacterium tuberculosis. The utility of bioluminescent M. tuberculosis reporter strains for real-time in vitro and ex vivo assessment of drug and vaccine activity has been demonstrated but a simple, non-invasive, real-time surrogate marker to replace CFU counts for real-time evaluation of drug and vaccine efficacy in vivo has not been described. We describe the development of a fully virulent and stable autoluminescent strain of M. tuberculosis and proof-of-concept experiments demonstrating its utility for in vivo bioluminescence imaging to assess the efficacy of new drugs and vaccines for tuberculosis in a mouse model. Relative light unit (RLU) counts paralleled CFU counts during the active phase of bacterial growth, with a lower limit of detection of approximately 10(6) CFU in live, anesthetized mice. Experiments distinguishing active from inactive anti-tuberculosis drugs and bacteriostatic drug effects from bactericidal effects were completed in less than 5 days. The ability of a recombinant BCG vaccine to limit bacterial growth was demonstrated within 3 weeks. Use of this autoluminescent reporter strain has the potential to drastically reduce the time, effort, animals and costs consumed in the evaluation of drug activity in vitro and the in vivo assessment of drug and vaccine efficacy. Public Library of Science 2012-01-11 /pmc/articles/PMC3256174/ /pubmed/22253776 http://dx.doi.org/10.1371/journal.pone.0029774 Text en Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhang, Tianyu
Li, Si-Yang
Nuermberger, Eric L.
Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title_full Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title_fullStr Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title_full_unstemmed Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title_short Autoluminescent Mycobacterium tuberculosis for Rapid, Real-Time, Non-Invasive Assessment of Drug and Vaccine Efficacy
title_sort autoluminescent mycobacterium tuberculosis for rapid, real-time, non-invasive assessment of drug and vaccine efficacy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256174/
https://www.ncbi.nlm.nih.gov/pubmed/22253776
http://dx.doi.org/10.1371/journal.pone.0029774
work_keys_str_mv AT zhangtianyu autoluminescentmycobacteriumtuberculosisforrapidrealtimenoninvasiveassessmentofdrugandvaccineefficacy
AT lisiyang autoluminescentmycobacteriumtuberculosisforrapidrealtimenoninvasiveassessmentofdrugandvaccineefficacy
AT nuermbergerericl autoluminescentmycobacteriumtuberculosisforrapidrealtimenoninvasiveassessmentofdrugandvaccineefficacy