skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Cytokinin Signaling in Mycobacterium tuberculosis

Journal Article · · mBio (Online)
 [1];  [2];  [3];  [4];  [4];  [1];  [1];  [5];  [6];  [4];  [2];  [1];  [7];  [8]
  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)
+ Show Author Affiliations

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.

Research Organization:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0012704
OSTI ID:
1491698
Report Number(s):
BNL-210895-2019-JAAM
Journal Information:
mBio (Online), Vol. 9, Issue 3; ISSN 2150-7511
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 23 works
Citation information provided by
Web of Science

References (43)

In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice journal December 2007
Mycolic Acid Cyclopropanation is Essential for Viability, Drug Resistance, and Cell Wall Integrity of Mycobacterium tuberculosis journal May 2009
CYTOKININS: Activity, Biosynthesis, and Translocation journal June 2006
Overview of the CCP 4 suite and current developments journal March 2011
A new evolutionary scenario for the Mycobacterium tuberculosis complex journal March 2002
Deletion of a Mycobacterium tuberculosis Proteasomal ATPase Homologue Gene Produces a Slow‐Growing Strain That Persists in Host Tissues
  • Lamichhane, Gyanu; Raghunand, Tirumalai R.; Morrison, Norman E.
  • The Journal of Infectious Diseases, Vol. 194, Issue 9 https://doi.org/10.1086/508288
journal November 2006
The Antituberculosis Drug Ethionamide Is Activated by a Flavoprotein Monooxygenase journal January 2002
Lipidomic analyses of Mycobacterium tuberculosis based on accurate mass measurements and the novel “ Mtb LipidDB” journal February 2011
Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420 journal March 2017
Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis journal August 2000
Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system journal March 2000
Specialized transduction: an efficient method for generating marked and unmarked targeted gene disruptions in Mycobacterium tuberculosis, M. bovis BCG and M. smegmatis journal October 2002
Identification of CRE1 as a cytokinin receptor from Arabidopsis journal February 2001
Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis: Pup conjugation pathway journal August 2010
The Proteasome of Mycobacterium tuberculosis Is Required for Resistance to Nitric Oxide journal December 2003
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
GenoList: an integrated environment for comparative analysis of microbial genomes journal December 2007
α/β Hydrolase fold enzymes: the family keeps growing journal December 1999
A bioanalytical method to determine the cell wall composition of Mycobacterium tuberculosis grown in vivo journal February 2012
Evolution of cytokinin biosynthesis and degradation journal February 2011
Cytokinin signaling: two-components and more journal February 2008
Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice journal March 2007
p -Hydroxybenzoic Acid Synthesis in Mycobacterium tuberculosis journal October 2005
New use of BCG for recombinant vaccines journal June 1991
Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the Mycobacterium tuberculosis repressor EthR2 journal May 2017
Structural basis for cytokinin receptor signaling: an evolutionary approach journal March 2013
Phospholipid:diacylglycerol acyltransferase-mediated triacylglycerol biosynthesis is crucial for protection against fatty acid-induced cell death in growing tissues of Arabidopsis journal November 2013
The Mycobacterium tuberculosis Proteasome Active Site Threonine Is Essential for Persistence Yet Dispensable for Replication and Resistance to Nitric Oxide journal August 2010
Proteasomal Control of Cytokinin Synthesis Protects Mycobacterium tuberculosis against Nitric Oxide journal March 2015
A Comparative Lipidomics Platform for Chemotaxonomic Analysis of Mycobacterium tuberculosis journal December 2011
Granuloma-Specific Expression of Mycobacterium Virulence Proteins from the Glycine-Rich PE-PGRS Family journal May 2000
Bacterial expression, purification of full length and carboxyl terminal fragment of alzheimer amyloid precursor protein and their proteolytic processing by thrombin journal January 1994
The HHpred interactive server for protein homology detection and structure prediction journal July 2005
Characterization of the Proteasome Accessory Factor (paf) Operon in Mycobacterium tuberculosis journal February 2007
A novel copper-responsive regulon in Mycobacterium tuberculosis: RicR regulon in Mycobacterium tuberculosis journal October 2010
A Novel In Vitro Multiple-Stress Dormancy Model for Mycobacterium tuberculosis Generates a Lipid-Loaded, Drug-Tolerant, Dormant Pathogen journal June 2009
The Copper-Responsive RicR Regulon Contributes to Mycobacterium tuberculosis Virulence journal February 2014
Inhibitors selective for mycobacterial versus human proteasomes journal September 2009
Mycobacterium tuberculosis appears to lack α-ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes: Pyruvate dehydrogenase of Mycobacterium tuberculosis journal June 2005
TM4: A Free, Open-Source System for Microarray Data Management and Analysis journal February 2003
Cavin1 intrinsically disordered domains are essential for fuzzy electrostatic interactions and caveola formation journal February 2021
Overview of the CCP4 suite and current developments. text January 2011
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010

Cited By (1)

The Synthesis of 3H-Labelled 8-Azido-N6-Benzyladenine and Related Compounds for Photoaffinity Labelling of Cytokinin-Binding Proteins journal January 2019

Figures / Tables (9)

Table 1(p. 28)table Table 1
Table 2(p. 33)table Table 2
Table 3(p. 34)table Table 3
D) Dose-dependent production of Rv0077c protein. Bacteria were incubated with cytokinin at the indicated concentrations for 24 hours. (E) Only cytokinins, and not closely related molecules, induce the production of Rv0077c. Each compound was added to a final concentration of 100 μM. "R" indicates the riboside form of the preceding indicated cytokinin. (F) Adenine inhibits the induction of Rv0077c by 100 μM iP. For all panels, we added an equal volume of DMSO to samples where iP was not added. For all immunoblots (IB), we stripped the membranes and incubated them with antibodies to dihydrolipoamide acyltransferase (DlaT) to confirm equal loading of total lysates. Molecular weight standards are indicated to the left of the blots and are in kilodaltons (kD). Ade, adenine." data-ostiid="1491698">
Fig. 1(p. 42)figure Fig. 1
Fig. 2(p. 43)figure Fig. 2
Fig. 3(p. 44)figure Fig. 3
Fig. 4(p. 45)figure Fig. 4
Fig. 5(p. 46)figure Fig. 5
Fig. 6(p. 47)figure Fig. 6

Similar Records

Cytokinin Signaling in Mycobacterium tuberculosis
Journal Article · Tue Jun 19 00:00:00 EDT 2018 · mBio (Online) · OSTI ID:1491698
+11 more
The Mycobacterium tuberculosis desaturase DesA1 (Rv0824c) is a Ca{sup 2+} binding protein
Journal Article · Fri Nov 04 00:00:00 EDT 2016 · Biochemical and Biophysical Research Communications · OSTI ID:1491698
+1 more
Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis
Journal Article · Wed Aug 24 00:00:00 EDT 2011 · Mol. Microbiol. · OSTI ID:1491698
+4 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Mycobacterium tuberculosis
acid-fast staining
cytokinin
regulation
signaling