Mapping and manipulating the Mycobacterium tuberculosis transcriptome using a transcription factor...

Area of Science:

• Microbiology
• Systems Biology
• Genomics

Background:

• Mycobacterium tuberculosis (M.tb) adapts to host environments through complex gene regulation.
• Understanding the gene regulatory network is crucial for combating tuberculosis.

Purpose of the Study:

• To comprehensively map the gene regulatory network of M.tb.
• To characterize the transcriptional consequences of overexpressing individual transcription factors.

Main Methods:

• Overexpression of 206 transcription factors in M.tb using an inducible promoter.
• Global transcriptional profiling of engineered M.tb strains.
• Computational modeling to predict phenotypes and growth rates.

Main Results:

• Identified 9,335 regulatory consequences for 183 transcription factors, covering 70% of the M.tb genome.
• Overexpression of transcription factors primarily repressed basal transcription.
• Predicted and validated a regulator influencing isoniazid susceptibility.
• Accurately predicted M.tb growth rates using combined data.

Conclusions:

• Developed a systems-level framework for the M.tb transcriptome.
• Characterized the influence of nearly all M.tb transcription factors.
• Demonstrated the utility of this resource for future research into M.tb pathogenesis and adaptation.