Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis.

Matthew Silcocks; James P Lingford; Chen-Yi Cheung; William J Jowsey; Rita M McCall; Christopher D Rae; Liam K Harold; David Edwards; Evan Pepper-Tunick; Stephanie L Neville; Megan J Maher; Aleix Canalda-Baltrons; Xuling Chang; Phan Vuong Khac Thai; Kathryn E Holt; Nitin S Baliga; Gregory M Cook; Thomas R Hawn; Nguyen Thuy Thuong Thuong; Maxine Caws; Chris Greening; Christopher A McDevitt; Jeffery S Cox; Matthew B McNeil; Sarah J Dunstan

Journal article

Dormancy regulon reduction was pivotal to the evolution of Mycobacterium tuberculosis.

Matthew Silcocks, James P Lingford, Chen-Yi Cheung, William J Jowsey, Rita M McCall, Christopher D Rae, Liam K Harold, David Edwards, Evan Pepper-Tunick, Stephanie L Neville, Megan J Maher, Aleix Canalda-Baltrons, Xuling Chang, Phan Vuong Khac Thai, Kathryn E Holt, Nitin S Baliga, Gregory M Cook, Thomas R Hawn, Nguyen Thuy Thuong Thuong, Maxine Caws Show all

Nat Commun | Published : 2026

DOI: 10.1038/s41467-026-71566-x

Abstract

Phenotypically agnostic screens for positive selection in pathogen populations provide a means of pinpointing genes and regulatory regions involved in adaptation to the local environment or host population. We screened a large (n = 2506) collection of Vietnamese Mycobacterium tuberculosis (Mtb) isolates, finding targets of selection to be lineage-specific, and encompass diverse functions, including dormancy (Rv0080), zinc homeostasis (zur), and virulence (ESX-1 structure). Extending our screen to the wider Mtb complex (MTBC) phylogeny demonstrated Rv0080 to display an extraordinarily dynamic evolutionary history, acquiring premature stop codons or putative functional mutations on branches up..

View full abstract