Characterization and transcriptome analysis of Mycobacterium tuberculosis persisters.

Area of Science:

• Microbiology
• Molecular Biology
• Public Health

Background:

• Tuberculosis (TB) remains a significant global health challenge.
• Long treatment durations and latent infections hinder TB control efforts.
• Drug-tolerant persister cells in Mycobacterium tuberculosis may cause treatment difficulties.

Purpose of the Study:

• To investigate the prevalence and characteristics of Mycobacterium tuberculosis persister cells.
• To analyze the gene expression profile of persister cells.
• To identify potential core dormancy response genes.

Main Methods:

• Quantification of persister cells during different growth phases (lag, exponential, stationary).
• Isolation of persister cells using d-cycloserine treatment and centrifugation.
• Transcriptome analysis of persister cells via Affymetrix arrays.

Main Results:

• Persister cell numbers increase significantly in late exponential and stationary phases, comprising ~1% of the population.
• Persister cell transcriptomes show downregulated metabolic and biosynthetic pathways, indicating dormancy.
• A subset of genes is upregulated in persisters, potentially involved in their formation and maintenance.

Conclusions:

• Persister formation in Mycobacterium tuberculosis involves both stochastic and deterministic mechanisms.
• The identified upregulated genes in persisters may be crucial for their survival.
• A core dormancy response involving specific genes might exist across different in vitro dormancy models.