Transcriptomic responses to antibiotic exposure in Mycobacterium tuberculosis

Area of Science:

• Microbiology
• Genomics
• Pharmacology

Background:

• Bacterial transcriptional responses to antibiotics provide insights into drug mechanisms and resistance.
• Understanding these responses in Mycobacterium tuberculosis (Mtb) is crucial for developing effective treatments.

Purpose of the Study:

• To define the transcriptional antibiotic response (TAR) in Mtb isolates for clinically relevant drugs.
• To analyze Mtb microarray and RNA-seq data sets to characterize TAR.

Main Methods:

• Pooled and analyzed Mtb microarray and RNA-seq data sets.
• Generated 99 antibiotic transcription profiles across 17 antibiotics.
• Utilized varying exposure times (3-24 hours) and concentrations relative to WHO critical concentrations.

Main Results:

• Transcriptional antibiotic response (TAR) genes were time-dependent and specific to antibiotic mechanisms.
• TAR signatures demonstrated high accuracy in predicting antibiotic exposure (AUC 0.76-1.00).
• Transcriptomics allows assessment of antibiotic activity in Mtb within 6 hours.

Conclusions:

• Transcriptional profiling is a valuable tool for studying Mtb antibiotic responses.
• TAR signatures can be used to rapidly assess antibiotic efficacy.
• This approach aids in understanding antimicrobial resistance mechanisms in Mtb.