Genetically encoded transcriptional plasticity underlies stress adaptation in Mycobacterium tuberculosis

Abstract

Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) remains largely unexplored. In this study, we investigate the genome-wide TP profiles ofMycobacterium tuberculosis(Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal thatMtbgenes exhibit significant TP variation that correlates with gene function and gene essentiality. We also found that critical genetic features, such as gene length, GC content, and operon size independently impose constraints on TP, beyond trans-regulation. By extending our analysis to include two otherMycobacteriumspecies --M. smegmatisandM. abscessus -- we demonstrate a striking conservation of the TP landscape. This study provides a comprehensive understanding of the TP exhibited by mycobacteria genes, shedding light on this significant, yet understudied, genetic feature encoded in bacterial genomes.

Structural insights into transcription regulation of the global virulence factor PhoP fromMycobacterium tuberculosis

“…This complex stress adaptation mechanism leads to diverse gene variability which is generally termed as transcriptional plasticity. Recently, transcriptomic analysis of Mtb genome under a multitude of environmental pressures points out that the profile of significant transcriptional plasticity closely correlates with transcription regulators, possible promoter features and relevant regulatory mechanisms 33 . However, the intricate molecular mechanisms underlying such stress adaptation are still obscure.…”