Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis
Summary: Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB dur...
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doaj-c019f6341eab44dc908e3aa1afddd8022020-11-25T03:00:40ZengElsevierCell Reports2211-12472020-04-01314Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosisEliza J.R. Peterson0Abrar A. Abidi1Mario L. Arrieta-Ortiz2Boris Aguilar3James T. Yurkovich4Amardeep Kaur5Min Pan6Vivek Srinivas7Ilya Shmulevich8Nitin S. Baliga9Institute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USAInstitute for Systems Biology, Seattle, WA 98109, USA; Molecular and Cellular Biology Program, Departments of Microbiology and Biology, University of Washington, Seattle, WA; Lawrence Berkeley National Laboratories, Berkeley, CA; Corresponding authorSummary: Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB during disease latency and reactivation has posed a challenge. We develop an experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding map and insights from network topology analysis, we identify regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions. : Mycobacterium tuberculosis (MTB) persists within the host by counteracting disparate stressors including hypoxia. Peterson et al. report a transcriptional program that coordinates sequential state transitions to drive MTB in and out of hypoxia-induced dormancy. Among varied properties, this program encodes advanced preparedness to infect the host in favorable conditions. Keywords: Mycobacterium tuberculosis, hypoxia, granuloma, dormancy, gene regulatory network, regulatory motifs, transcriptional state, reactor, systems biology, state transitionhttp://www.sciencedirect.com/science/article/pii/S221112472030526X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eliza J.R. Peterson Abrar A. Abidi Mario L. Arrieta-Ortiz Boris Aguilar James T. Yurkovich Amardeep Kaur Min Pan Vivek Srinivas Ilya Shmulevich Nitin S. Baliga |
spellingShingle |
Eliza J.R. Peterson Abrar A. Abidi Mario L. Arrieta-Ortiz Boris Aguilar James T. Yurkovich Amardeep Kaur Min Pan Vivek Srinivas Ilya Shmulevich Nitin S. Baliga Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis Cell Reports |
author_facet |
Eliza J.R. Peterson Abrar A. Abidi Mario L. Arrieta-Ortiz Boris Aguilar James T. Yurkovich Amardeep Kaur Min Pan Vivek Srinivas Ilya Shmulevich Nitin S. Baliga |
author_sort |
Eliza J.R. Peterson |
title |
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis |
title_short |
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis |
title_full |
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis |
title_fullStr |
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis |
title_full_unstemmed |
Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis |
title_sort |
intricate genetic programs controlling dormancy in mycobacterium tuberculosis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-04-01 |
description |
Summary: Mycobacterium tuberculosis (MTB) displays the remarkable ability to transition in and out of dormancy, a hallmark of the pathogen’s capacity to evade the immune system and exploit susceptible individuals. Uncovering the gene regulatory programs that underlie the phenotypic shifts in MTB during disease latency and reactivation has posed a challenge. We develop an experimental system to precisely control dissolved oxygen levels in MTB cultures in order to capture the transcriptional events that unfold as MTB transitions into and out of hypoxia-induced dormancy. Using a comprehensive genome-wide transcription factor binding map and insights from network topology analysis, we identify regulatory circuits that deterministically drive sequential transitions across six transcriptionally and functionally distinct states encompassing more than three-fifths of the MTB genome. The architecture of the genetic programs explains the transcriptional dynamics underlying synchronous entry of cells into a dormant state that is primed to infect the host upon encountering favorable conditions. : Mycobacterium tuberculosis (MTB) persists within the host by counteracting disparate stressors including hypoxia. Peterson et al. report a transcriptional program that coordinates sequential state transitions to drive MTB in and out of hypoxia-induced dormancy. Among varied properties, this program encodes advanced preparedness to infect the host in favorable conditions. Keywords: Mycobacterium tuberculosis, hypoxia, granuloma, dormancy, gene regulatory network, regulatory motifs, transcriptional state, reactor, systems biology, state transition |
url |
http://www.sciencedirect.com/science/article/pii/S221112472030526X |
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