ArticleJournal of bacteriology2017
Effects of Increasing the Affinity of CarD for RNA Polymerase on Mycobacterium tuberculosis Growth, rRNA Transcription, and Virulence.
Article in Journal of bacteriology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Single-Molecule Methods to Investigate Mechanisms of Transcription by RNA Polymerase ofbioRxiv : the preprint server for biology · 2026Article
- Expanding the CarD interaction network: CrsL is a novel transcription regulator in actinobacteria.Nucleic acids research · 2025Article
- Structural Insights into De Novo Promoter Escape by Mycobacterium tuberculosis RNA Polymerase.Nature communications · 2025Article
- Regulation of the transcription factor CdnL promotes adaptation to nutrient stress inPNAS nexus · 2024Article
- Regulation of the transcription factor CdnL promotes adaptation to nutrient stress inbioRxiv : the preprint server for biology · 2023Article
- Article
- Proteomic Signatures of Microbial Adaptation to the Highest Ultraviolet-Irradiation on Earth: Lessons From a Soil Actinobacterium.Frontiers in microbiology · 2022Article
- Transcriptional control of mycobacterial DNA damage response by sigma adaptation.Science advances · 2021Article
- CarD contributes to diverse gene expression outcomes throughout the genome ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural, functional and biological insights into the role of Mycobacterium tuberculosis VapBC11 toxin-antitoxin system: targeting a tRNase to tackle mycobacterial adaptation.Nucleic acids research · 2018Article
- Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils.Scientific reports · 2018Article
- Domains within RbpA Serve Specific Functional Roles That Regulate the Expression of Distinct Mycobacterial Gene Subsets.Journal of bacteriology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
CarD is an essential RNA polymerase (RNAP) interacting protein in Mycobacterium tuberculosis that stimulates formation of RNAP-promoter open complexes. CarD plays a complex role in M. tuberculosis growth and virulence that is not fully understood. Therefore, to gain further insight into the role of CarD in M. tuberculosis growth and virulence, we determined the effect of increasing the affinity of CarD for RNAP. Using site-directed mutagenesis guided by crystal structures of CarD bound to RNAP, we identified amino acid substitutions that increase the affinity of CarD for RNAP. Using these substitutions, we show that increasing the affinity of CarD for RNAP increases the stability of the CarD protein in M. tuberculosis In addition, we show that increasing the affinity of CarD for RNAP increases the growth rate in M. tuberculosis without affecting 16S rRNA levels. We further show that increasing the affinity of CarD for RNAP reduces M. tuberculosis virulence in a mouse model of infection despite the improved growth rate in vitro Our findings suggest that the CarD-RNAP interaction protects CarD from proteolytic degradation in M. tuberculosis, establish that growth rate and rRNA levels can be uncoupled in M. tuberculosis and demonstrate that the strength of the CarD-RNAP interaction has been finely tuned to optimize virulence. IMPORTANCE: Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a major global health problem. In order to develop new strategies to battle this pathogen, we must gain a better understanding of the molecular processes involved in its survival and pathogenesis. We have previously identified CarD as an essential transcriptional regulator in mycobacteria. In this study, we detail the effects of increasing the affinity of CarD for RNAP on transcriptional regulation, CarD protein stability, and virulence. These studies expand our understanding of the global transcription regulator CarD, provide insight into how CarD activity is regulated, and broaden our understanding of prokaryotic transcription.
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Registered trials
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.