1887

Abstract

employs two-component systems (TCSs) for survival within its host. The TCS MtrAB is conserved among mycobacteria. The response regulator MtrA is essential in . The genome-wide chromatin immunoprecipitation (ChIP) sequencing performed in this study suggested that MtrA binds upstream of at least 45 genes of , including those involved in cell wall remodelling, stress responses, persistence and regulation of transcription. It binds to the promoter regions and regulates the peptidoglycan hydrolases and , which are required for resuscitation from dormancy. It also regulates the expression of , a critical regulator of the oxidative stress response, and , one-half of the toxin–antitoxin locus . We have identified a new consensus 9 bp loose motif for MtrA binding. Mutational changes in the consensus sequence greatly reduced the binding of MtrA to its newly identified targets. Importantly, we observed that overexpression of a gain-of-function mutant, MtrAY102C, enhanced expression of the aforesaid genes in isolated from macrophages, whereas expression of each of these targets was lower in overexpressing a phosphorylation-defective mutant, MtrAD56N. This result suggests that phosphorylated MtrA (MtrA-P) is required for the expression of its targets in macrophages. Our data have uncovered new MtrA targets that suggest that MtrA is required for a transcriptional response that likely enables to persist within its host and emerge out of dormancy when the conditions are favourable.

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2018-01-01
2024-12-08
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