PUBLICATION
Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in Zebrafish
- Authors
- Chen, Z., Hu, Y., Cumming, B.M., Lu, P., Feng, L., Deng, J., Steyn, A.J., Chen, S.
- ID
- ZDB-PUB-160823-5
- Date
- 2016
- Source
- Cell Reports 16(9): 2512-24 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Aerobiosis/genetics
- Amino Acid Sequence
- Anaerobiosis/genetics
- Animals
- Bacterial Proteins/genetics*
- Bacterial Proteins/metabolism
- Fish Diseases/microbiology
- Fish Diseases/pathology
- Gene Expression Regulation, Bacterial*
- Granuloma/microbiology
- Granuloma/pathology
- Granuloma/veterinary
- Host-Pathogen Interactions
- Iron-Sulfur Proteins/chemistry
- Iron-Sulfur Proteins/genetics*
- Iron-Sulfur Proteins/metabolism
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium Infections, Nontuberculous/pathology
- Mycobacterium marinum/drug effects
- Mycobacterium marinum/genetics*
- Mycobacterium marinum/growth & development
- Mycobacterium marinum/pathogenicity
- Nitric Oxide/chemistry
- Nitric Oxide/pharmacology
- Nitric Oxide Donors/chemistry
- Nitric Oxide Donors/pharmacology
- Protein Kinases/genetics
- Protein Kinases/metabolism
- Regulon*
- Sequence Alignment
- Sequence Homology, Amino Acid
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Transcriptome
- Triazenes/chemistry
- Triazenes/pharmacology
- Virulence
- Zebrafish/microbiology
- PubMed
- 27545883 Full text @ Cell Rep.
Citation
Chen, Z., Hu, Y., Cumming, B.M., Lu, P., Feng, L., Deng, J., Steyn, A.J., Chen, S. (2016) Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in Zebrafish. Cell Reports. 16(9):2512-24.
Abstract
During the course of infection, Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. How these stressors are sensed and relayed to the Mtb transcriptional apparatus remains unclear. Here, we provide evidence that WhiB6 differentially regulates the ESX-1 and DosR regulons through its Fe-S cluster. When challenged with NO, WhiB6 continually activates expression of the DosR regulons but regulates ESX-1 expression through initial activation followed by gradual inhibition. Comparative transcriptomic analysis of the holo- and reduced apo-WhiB6 complemented strains confirms these results and also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division, and virulence. Using the Mycobacterium marinum zebrafish infection model, we find that holo- and apo-WhiB6 modulate levels of mycobacterial infection, granuloma formation, and dissemination. These findings provide fresh insight into the role of WhiB6 in mycobacterial infection, dissemination, and disease development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping