Related Experiment Video

Updated: Jun 26, 2025

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1
07:42

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1

Published on: February 28, 2025

308

Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level

Hina Khan1, Partha Paul1, Harsh Goar1

  • 1CSIR, Institute of Microbial Technology, Chandigarh, India.

Elife
|May 13, 2024
PubMed

Insights

Mycobacterium tuberculosis survival relies on the PhoP regulator. PhoP controls cyclic adenosine monophosphate (cAMP) levels by repressing Rv0805, a phosphodiesterase, impacting bacterial stress tolerance and survival.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pathogenesis

Background:

  • Survival of Mycobacterium tuberculosis within host macrophages is crucial for disease persistence.
  • The virulence regulator PhoP is essential for M. tuberculosis survival, but its precise role is unclear.
  • Cyclic adenosine monophosphate (cAMP) acts as a second messenger influencing microbial pathogen responses.

Purpose of the Study:

  • To investigate the role of PhoP in regulating intracellular cAMP levels in M. tuberculosis.
  • To elucidate the mechanism by which PhoP influences bacterial stress tolerance and survival.

Main Methods:

  • Transcriptomic analysis to identify PhoP-regulated genes.
  • Electrophoretic mobility shift assays (EMSA) to confirm PhoP binding to the rv0805 promoter.
  • Genetic manipulation of M. tuberculosis to inactivate PhoP or overexpress Rv0805.
  • Measurement of intracellular cAMP levels.

Main Results:

  • PhoP acts as a repressor of the cAMP-specific phosphodiesterase Rv0805.
  • PhoP directly binds to the promoter region of the rv0805 gene.
  • Deletion of phoP or ectopic expression of rv0805 leads to decreased intracellular cAMP levels.
  • Inactivation of the PhoP-Rv0805-cAMP pathway reduces M. tuberculosis stress tolerance and intracellular survival.

Conclusions:

  • PhoP regulates M. tuberculosis intracellular cAMP levels by repressing Rv0805 phosphodiesterase activity.
  • The PhoP-mediated control of cAMP is critical for bacterial stress adaptation and survival within macrophages.
  • Targeting this pathway could offer novel strategies for tuberculosis treatment.
Keywords:
MycobacteriumPhoPcAMP levelinfectious diseasemicrobiologystress responsevirulence regulation

More Related Videos

Preparation of Mycobacterium Tuberculosis Culture Filtrate to Understand TB Pathogenesis07:32

Preparation of Mycobacterium Tuberculosis Culture Filtrate to Understand TB Pathogenesis

Published on: March 28, 2025

374
Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa11:31

Establishment of a High-throughput Setup for Screening Small Molecules That Modulate c-di-GMP Signaling in Pseudomonas aeruginosa

Published on: June 30, 2016

8.6K

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
Intracellular Signaling Cascades01:24

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
46.7K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.5K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K