ArticlePLoS genetics2022
PrrA modulates Mycobacterium tuberculosis response to multiple environmental cues and is critically regulated by serine/threonine protein kinases.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Cefpiramide RestrictsACS medicinal chemistry letters · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway with Mycobacterium tuberculosis adaptation to nitric oxide and iron limitation stress.PLoS genetics · 2026Article
- Rv3839-Rv3840 links the endogenous heme biosynthesis pathway withbioRxiv : the preprint server for biology · 2026Article
- Serine/threonine protein kinase phosphorylation of DosR alters target gene transcription mechanics and regulates Mycobacterium tuberculosis response to nitric oxide stress.PLoS genetics · 2026Article
- Multiple input-multiple output (MIMO) designs in two-component signalling systems of Mycobacterium tuberculosis.FEMS microbiology reviews · 2026Review
- STK-mediated FadR phosphorylation regulates the acid resistance and virulence of Streptococcus suis.PLoS pathogens · 2025Article
- Mycobacterial MutT1-mediated dephosphorylation of the sensor histidine kinases reveals a new link in the regulation of the two-component signaling.Nucleic acids research · 2025Article
- Cholesterol metabolism and intrabacterial potassium homeostasis are intrinsically related in Mycobacterium tuberculosis.PLoS pathogens · 2025Article
- Article
- Harnessing hypoxia: bacterial adaptation and chronic infection in cystic fibrosis.FEMS microbiology reviews · 2025Review
- Comprehensive whole metagenomics analysis uncovers microbial community and resistome variability across anthropogenically contaminated soils in urban and suburban areas of Tamil Nadu, India.Frontiers in microbiology · 2025Article
- Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages.Scientific reports · 2024Article
- Review
- TargetingMicrobiology (Reading, England) · 2024Review
- Regulatory Intersection of Two-component System and Ser/Thr Protein Kinase Signaling in Mycobacterium tuberculosis.Journal of molecular biology · 2024Article
- Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator.PLoS genetics · 2024Article
- Clinically relevant mutations in the PhoR sensor kinase of host-adaptedMicrobiology spectrum · 2023Article
- Dual functioning by the PhoR sensor is a key determinant to Mycobacterium tuberculosis virulence.PLoS genetics · 2023Article
- Shining a light on bacterial environmental cue integration and its relation to metabolism.Molecular microbiology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ability of Mycobacterium tuberculosis (Mtb) to adapt to its surrounding environment is critical for the bacterium to successfully colonize its host. Transcriptional changes are a vital mechanism by which Mtb responds to key environmental signals experienced, such as pH, chloride (Cl-), nitric oxide (NO), and hypoxia. However, much remains unknown regarding how Mtb coordinates its response to the disparate signals seen during infection. Utilizing a transcription factor (TF) overexpression plasmid library in combination with a pH/Cl--responsive luciferase reporter, we identified the essential TF, PrrA, part of the PrrAB two-component system, as a TF involved in modulation of Mtb response to pH and Cl-. Further studies revealed that PrrA also affected Mtb response to NO and hypoxia, with prrA overexpression dampening induction of NO and hypoxia-responsive genes. PrrA is phosphorylated not just by its cognate sensor histidine kinase PrrB, but also by serine/threonine protein kinases (STPKs) at a second distinct site. Strikingly, a STPK-phosphoablative PrrA variant was significantly dampened in its response to NO versus wild type Mtb, disrupted in its ability to adaptively enter a non-replicative state upon extended NO exposure, and attenuated for in vivo colonization. Together, our results reveal PrrA as an important regulator of Mtb response to multiple environmental signals, and uncover a critical role of STPK regulation of PrrA in its function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.