Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters

ABSTRACT Tuberculosis continues to be a major public health problem in many parts of the world. Significant obstacles in controlling the epidemic are the length of treatment and the large reservoir of latently infected people. Bacteria form dormant, drug-tolerant persister cells, which may be respon...

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Autores principales:	Iris Keren, Shoko Minami, Eric Rubin, Kim Lewis
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/260a566633a241c7b4474cfc8b4620f8
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spelling	oai:doaj.org-article:260a566633a241c7b4474cfc8b4620f82021-11-15T15:38:50ZCharacterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters10.1128/mBio.00100-112150-7511https://doaj.org/article/260a566633a241c7b4474cfc8b4620f82011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00100-11https://doaj.org/toc/2150-7511ABSTRACT Tuberculosis continues to be a major public health problem in many parts of the world. Significant obstacles in controlling the epidemic are the length of treatment and the large reservoir of latently infected people. Bacteria form dormant, drug-tolerant persister cells, which may be responsible for the difficulty in treating both acute and latent infections. We find that in Mycobacterium tuberculosis, low numbers of drug-tolerant persisters are present in lag and early exponential phases, increasing sharply at late exponential and stationary phases to make up ~1% of the population. This suggests that persister formation is governed by both stochastic and deterministic mechanisms. In order to isolate persisters, an exponentially growing population was treated with d-cycloserine, and cells surviving lysis were collected by centrifugation. A transcriptome of persisters was obtained by using hybridization to an Affymetrix array. The transcriptome shows downregulation of metabolic and biosynthetic pathways, consistent with a certain degree of dormancy. A set of genes was upregulated in persisters, and these are likely involved in persister formation and maintenance. A comparison of the persister transcriptome with transcriptomes obtained for several in vitro dormancy models identified a small number of genes upregulated in all cases, which may represent a core dormancy response. IMPORTANCE It is estimated that every third person on the planet is infected with Mycobacterium tuberculosis. The two major problems in controlling M. tuberculosis are the length of the treatment and the large reservoir of latently infected people. Dormant persister cells may be responsible for both problems. We find that M. tuberculosis produces persisters in vitro in a growth phase-dependent manner. Persisters were isolated from an exponentially growing population, and their transcriptome shows a distinct pattern of dormancy. These results give the first insight into M. tuberculosis persisters and point to possible mechanisms responsible for their formation.Iris KerenShoko MinamiEric RubinKim LewisAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Iris Keren Shoko Minami Eric Rubin Kim Lewis Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
description	ABSTRACT Tuberculosis continues to be a major public health problem in many parts of the world. Significant obstacles in controlling the epidemic are the length of treatment and the large reservoir of latently infected people. Bacteria form dormant, drug-tolerant persister cells, which may be responsible for the difficulty in treating both acute and latent infections. We find that in Mycobacterium tuberculosis, low numbers of drug-tolerant persisters are present in lag and early exponential phases, increasing sharply at late exponential and stationary phases to make up ~1% of the population. This suggests that persister formation is governed by both stochastic and deterministic mechanisms. In order to isolate persisters, an exponentially growing population was treated with d-cycloserine, and cells surviving lysis were collected by centrifugation. A transcriptome of persisters was obtained by using hybridization to an Affymetrix array. The transcriptome shows downregulation of metabolic and biosynthetic pathways, consistent with a certain degree of dormancy. A set of genes was upregulated in persisters, and these are likely involved in persister formation and maintenance. A comparison of the persister transcriptome with transcriptomes obtained for several in vitro dormancy models identified a small number of genes upregulated in all cases, which may represent a core dormancy response. IMPORTANCE It is estimated that every third person on the planet is infected with Mycobacterium tuberculosis. The two major problems in controlling M. tuberculosis are the length of the treatment and the large reservoir of latently infected people. Dormant persister cells may be responsible for both problems. We find that M. tuberculosis produces persisters in vitro in a growth phase-dependent manner. Persisters were isolated from an exponentially growing population, and their transcriptome shows a distinct pattern of dormancy. These results give the first insight into M. tuberculosis persisters and point to possible mechanisms responsible for their formation.
format	article
author	Iris Keren Shoko Minami Eric Rubin Kim Lewis
author_facet	Iris Keren Shoko Minami Eric Rubin Kim Lewis
author_sort	Iris Keren
title	Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
title_short	Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
title_full	Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
title_fullStr	Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
title_full_unstemmed	Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters
title_sort	characterization and transcriptome analysis of <named-content content-type="genus-species">mycobacterium tuberculosis</named-content> persisters
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/260a566633a241c7b4474cfc8b4620f8
work_keys_str_mv	AT iriskeren characterizationandtranscriptomeanalysisofnamedcontentcontenttypegenusspeciesmycobacteriumtuberculosisnamedcontentpersisters AT shokominami characterizationandtranscriptomeanalysisofnamedcontentcontenttypegenusspeciesmycobacteriumtuberculosisnamedcontentpersisters AT ericrubin characterizationandtranscriptomeanalysisofnamedcontentcontenttypegenusspeciesmycobacteriumtuberculosisnamedcontentpersisters AT kimlewis characterizationandtranscriptomeanalysisofnamedcontentcontenttypegenusspeciesmycobacteriumtuberculosisnamedcontentpersisters
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Characterization and Transcriptome Analysis of <named-content content-type="genus-species">Mycobacterium tuberculosis</named-content> Persisters

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