Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis

Peterson, Eliza J. R.; Abidi, Abrar A.; Arrieta-Ortiz, Mario L.; Aguilar, Boris; Yurkovich, James T.; Kaur, Amardeep; Pan, Min; Srinivas, Vivek; Shmulevich, Ilya; Baliga, Nitin S.

doi:10.1016/j.celrep.2020.107577

Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis

Journal Article · Tue Apr 28 00:00:00 EDT 2020 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2020.107577· OSTI ID:1816119

Peterson, Eliza J. R. ^[1]; Abidi, Abrar A. ^[2]; Arrieta-Ortiz, Mario L. ^[2]; Aguilar, Boris ^[2]; Yurkovich, James T. ^[2]; Kaur, Amardeep ^[2]; Pan, Min ^[2]; Srinivas, Vivek ^[2]; Shmulevich, Ilya ^[2]; Baliga, Nitin S. ^[3]

Inst. for Systems Biology, Seattle, WA (United States); OSTI
Inst. for Systems Biology, Seattle, WA (United States)
Inst. for Systems Biology, Seattle, WA (United States); Univ. of Washington, Seattle, WA (United States). Molecular and Cellular Biology Program; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institute of Allergy and Infectious Diseases (NIAID); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1816119

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 4 Vol. 31; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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Cited By (3)

Additional file 1 of Genome-scale analyses of transcriptional start sites in Mycobacterium marinum under normoxic and hypoxic conditions Huang, Shaojia; Zhou, Wei; Tang, Wei figshare https://doi.org/10.6084/m9.figshare.14379492.v1	dataset	January 2021
Additional file 2 of Genome-scale analyses of transcriptional start sites in Mycobacterium marinum under normoxic and hypoxic conditions Huang, Shaojia; Zhou, Wei; Tang, Wei figshare https://doi.org/10.6084/m9.figshare.14379495	dataset	January 2021
Additional file 3 of Genome-scale analyses of transcriptional start sites in Mycobacterium marinum under normoxic and hypoxic conditions Huang, Shaojia; Zhou, Wei; Tang, Wei figshare https://doi.org/10.6084/m9.figshare.14379498	dataset	January 2021

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Mycobacterium tuberculosis
dormancy
gene regulatory network
granuloma
hypoxia
reactor
regulatory motifs
state transition
systems biology
transcriptional state

Intricate Genetic Programs Controlling Dormancy in Mycobacterium tuberculosis

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