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Title: Cytokinin Signaling in Mycobacterium tuberculosis

Abstract

It was recently reported that the human-exclusive pathogen Mycobacterium tuberculosis secretes cytokinins, which had only been known as plant hormones. While cytokinins are well-established, adenine-based signaling molecules in plants, they have never been shown to participate in signal transduction in other kingdoms of life. M. tuberculosis is not known to interact with plants. Therefore, we tested the hypothesis that cytokinins trigger transcriptional changes within this bacterial species. Here, we show cytokinins induced the strong expression of the M. tuberculosis gene Rv0077c. We found that Rv0077c expression is repressed by a TetR-like transcriptional repressor, Rv0078. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of M. tuberculosis. Furthermore, while acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice, consistent with an unaltered mycolic acid profile of Rv0077c-expressing cells. Collectively, these findings show cytokinins signal transcriptional changes that can affect M. tuberculosis acid-fastness and that cytokinin signaling is no longer limited to the kingdom Plantae.

Authors:
 [1];  [2];  [3];  [4];  [4];  [1];  [1];  [5];  [6];  [4];  [2];  [1];  [7];  [8]
+ Show Author Affiliations
  1. New York Univ. School of Medicine, New York, NY (United States)
  2. Van Andel Research Institute, Grand Rapids, MI (United States)
  3. Human Longevity, Inc., San Diego, CA (United States); Regeneron Pharmaceuticals, Inc., Tarrytown, NY (United States)
  4. Colorado State Univ., Fort Collins, CO (United States)
  5. Institute of Experimental Botany ASCR and Palacky Univ., Olomouc (Czech Republic)
  6. Brookhaven National Lab. (BNL), Upton, NY (United States)
  7. Seattle Biomedical Research Institute, Seattle, WA (United States)
  8. Univ. of Washington, Seattle, WA (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1491698
Report Number(s):
BNL-210895-2019-JAAM
Journal ID: ISSN 2150-7511
Grant/Contract Number:  
SC0012704
Resource Type:
Accepted Manuscript
Journal Name:
mBio (Online)
Additional Journal Information:
Journal Name: mBio (Online); Journal Volume: 9; Journal Issue: 3; Journal ID: ISSN 2150-7511
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Mycobacterium tuberculosis; acid-fast staining; cytokinin; regulation; signaling

Citation Formats

Samanovic, Marie I., Hsu, Hao -Chi, Jones, Marcus B., Jones, Victoria, McNeil, Michael R., Becker, Samuel H., Jordan, Ashley T., Strnad, Miroslav, Xu, Changcheng, Jackson, Mary, Li, Huilin, Darwin, K. Heran, Sherman, David R., and Greenberg, E. Peter. Cytokinin Signaling in Mycobacterium tuberculosis. United States: N. p., 2018. Web. doi:10.1128/mBio.00989-18.
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Samanovic, Marie I., Hsu, Hao -Chi, Jones, Marcus B., Jones, Victoria, McNeil, Michael R., Becker, Samuel H., Jordan, Ashley T., Strnad, Miroslav, Xu, Changcheng, Jackson, Mary, Li, Huilin, Darwin, K. Heran, Sherman, David R., & Greenberg, E. Peter. Cytokinin Signaling in Mycobacterium tuberculosis. United States. https://doi.org/10.1128/mBio.00989-18
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Samanovic, Marie I., Hsu, Hao -Chi, Jones, Marcus B., Jones, Victoria, McNeil, Michael R., Becker, Samuel H., Jordan, Ashley T., Strnad, Miroslav, Xu, Changcheng, Jackson, Mary, Li, Huilin, Darwin, K. Heran, Sherman, David R., and Greenberg, E. Peter. Tue . "Cytokinin Signaling in Mycobacterium tuberculosis". United States. https://doi.org/10.1128/mBio.00989-18. https://www.osti.gov/servlets/purl/1491698.
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@article{osti_1491698,
title = {Cytokinin Signaling in Mycobacterium tuberculosis},
author = {Samanovic, Marie I. and Hsu, Hao -Chi and Jones, Marcus B. and Jones, Victoria and McNeil, Michael R. and Becker, Samuel H. and Jordan, Ashley T. and Strnad, Miroslav and Xu, Changcheng and Jackson, Mary and Li, Huilin and Darwin, K. Heran and Sherman, David R. and Greenberg, E. Peter},
abstractNote = {It was recently reported that the human-exclusive pathogen Mycobacterium tuberculosis secretes cytokinins, which had only been known as plant hormones. While cytokinins are well-established, adenine-based signaling molecules in plants, they have never been shown to participate in signal transduction in other kingdoms of life. M. tuberculosis is not known to interact with plants. Therefore, we tested the hypothesis that cytokinins trigger transcriptional changes within this bacterial species. Here, we show cytokinins induced the strong expression of the M. tuberculosis gene Rv0077c. We found that Rv0077c expression is repressed by a TetR-like transcriptional repressor, Rv0078. Strikingly, cytokinin-induced expression of Rv0077c resulted in a loss of acid-fast staining of M. tuberculosis. Furthermore, while acid-fast staining is thought to be associated with changes in the bacterial cell envelope and virulence, Rv0077c-induced loss of acid-fastness did not affect antibiotic susceptibility or attenuate bacterial growth in mice, consistent with an unaltered mycolic acid profile of Rv0077c-expressing cells. Collectively, these findings show cytokinins signal transcriptional changes that can affect M. tuberculosis acid-fastness and that cytokinin signaling is no longer limited to the kingdom Plantae.},
doi = {10.1128/mBio.00989-18},
journal = {mBio (Online)},
number = 3,
volume = 9,
place = {United States},
year = {Tue Jun 19 00:00:00 EDT 2018},
month = {Tue Jun 19 00:00:00 EDT 2018}
}
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https://doi.org/10.1128/mBio.00989-18
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Cited by: 23 works
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Figures / Tables:

Table 1 Table 1: Bacterial strains, plasmids, and primer sequences.
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    The Synthesis of 3H-Labelled 8-Azido-N6-Benzyladenine and Related Compounds for Photoaffinity Labelling of Cytokinin-Binding Proteins
    journal, January 2019

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