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Rip1 and PdtaR mutant transcriptional responses to Nitric oxide

UID: 10631

Publisher(s): Memorial Sloan Kettering Cancer Center

Description
BioProject Summary: "Analysis of the transcriptional response of M. tuberculosis Erdman lacking the Rip1 protease, the PdtaR response regulator, or both, to the NO donor DETA-NO"

Abstract summary: "Bacterial pathogens that infect phagocytic cells must deploy mechanisms that sense and neutralize host microbicidal effectors. For Mycobacterium tuberculosis, the causative agent of tuberculosis, these mechanisms allow the bacterium to rapidly adapt from aerosol transmission to initial growth in the lung alveolar macrophage. Here, we identify a branched signaling circuit in M. tuberculosis that controls growth in the lung through integrated direct sensing of copper ions and nitric oxide by coupled activity of the Rip1 intramembrane protease and the PdtaS/R two-component system. This circuit uses a two-signal mechanism to inactivate the PdtaS/PdtaR two-component system, which constitutively represses virulence gene expression. Cu and NO inhibit the PdtaS sensor kinase through a dicysteine motif in the N-terminal GAF domain. The NO arm of the pathway is further controlled by sequestration of the PdtaR RNA binding response regulator by an NO-induced small RNA, controlled by the Rip1 intramembrane protease. This coupled Rip1/PdtaS/PdtaR circuit controls NO resistance and acute lung infection in mice by relieving PdtaS/R-mediated repression of isonitrile chalkophore biosynthesis. These studies identify an integrated mechanism by which M. tuberculosis senses and resists macrophage chemical effectors to achieve pathogenesis."
Subject of Study
Mycobacterium tuberculosis
Subject(s)
Mycobacterium tuberculosis
Triazenes
Access via BioProject

Information about the experiment with access to sample data
Accession #: PRJNA719428

Access via SRA

RNA Sequence reads for 24 samples
Accession #: PRJNA719428

Access Restrictions
Free to All
Access Instructions
The NCBI BioProject and SRA databases provide open access to these files.
Associated Publications
Buglino J, Sankhe G, Lazar N, et al. Integrated sensing of host stresses by inhibition of a cytoplasmic two-component system controls M. tuberculosis acute lung infection. eLife. 2021; 10:e65351.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
FASTQ, SRA
Data Tool(s)
RNA Seq
Dataset Size
11.95 GB
Data Catalog Record Updated
2023-12-07