Genetically encoded transcriptional plasticity underlies stress adaptation in Mycobacterium tuberculosis

Cheng Bei, Junhao Zhu, Peter H. Culviner, Mingyu Gan, Eric J. Rubin, Sarah M. Fortune, Qian Gao () and Qingyun Liu ()
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Cheng Bei: Fudan University
Junhao Zhu: Harvard T. H. Chan School of Public Health
Peter H. Culviner: Harvard T. H. Chan School of Public Health
Mingyu Gan: National Children’s Medical Center
Eric J. Rubin: Harvard T. H. Chan School of Public Health
Sarah M. Fortune: Harvard T. H. Chan School of Public Health
Qian Gao: Fudan University
Qingyun Liu: Harvard T. H. Chan School of Public Health

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Transcriptional regulation is a critical adaptive mechanism that allows bacteria to respond to changing environments, yet the concept of transcriptional plasticity (TP) – the variability of gene expression in response to environmental changes – remains largely unexplored. In this study, we investigate the genome-wide TP profiles of Mycobacterium tuberculosis (Mtb) genes by analyzing 894 RNA sequencing samples derived from 73 different environmental conditions. Our data reveal that Mtb genes exhibit significant TP variation that correlates with gene function and gene essentiality. We also find 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 other Mycobacterium species -- M. smegmatis and M. 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.

Date: 2024
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DOI: 10.1038/s41467-024-47410-5

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