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Updated: May 27, 2025

Isolation and Characterization of Extracellular Vesicles Produced by Iron-limited Mycobacteria
Published on: October 31, 2019
Maintenance of cell wall remodeling and vesicle production are connected in Mycobacterium tuberculosis
Vivian C Salgueiro-Toledo1, Jorge Bertol2, Claude Gutierrez3
1Department of Preventive Medicine and Public Health and Microbiology, Universidad Autónoma de Madrid, Madrid, Spain.
Abstract:
Pathogenic and nonpathogenic mycobacteria secrete extracellular vesicles (EVs) under various conditions. EVs produced by Mycobacterium tuberculosis (Mtb) have raised significant interest for their potential in cell communication, nutrient acquisition, and immune evasion. However, the relevance of vesicle secretion during tuberculosis infection remains unknown due to the limited understanding of mycobacterial vesicle biogenesis. We have previously shown that a transposon mutant in the LCP-related gene virR (virR) manifested a strong attenuated phenotype during experimental macrophage and murine infections, concomitant to enhanced vesicle release. In this study, we aimed to understand the role of VirR in the vesicle production process in Mtb. We employ genetic, transcriptional, proteomics, ultrastructural, and biochemical methods to investigate the underlying processes explaining the enhanced vesiculogenesis phenomenon observed in the virR. Our results establish that VirR is critical to sustain proper cell permeability via regulation of cell envelope remodeling possibly through the interaction with similar cell envelope proteins, which control the link between peptidoglycan and arabinogalactan. These findings advance our understanding of mycobacterial extracellular vesicle biogenesis and suggest that these set of proteins could be attractive targets for therapeutic intervention.
Insights
Mycobacterium tuberculosis (Mtb) gene VirR regulates cell envelope permeability, impacting extracellular vesicle (EV) production. Understanding VirR
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Mycobacteria, including Mycobacterium tuberculosis (Mtb), secrete extracellular vesicles (EVs) involved in cell communication and immune evasion.
- The biogenesis and role of Mtb EVs during tuberculosis infection are poorly understood.
- A transposon mutant in the LCP-related gene virR exhibits an attenuated phenotype and increased EV release.
Purpose of the Study:
- To elucidate the role of the gene virR in the process of Mtb vesicle production.
- To investigate the mechanisms underlying the enhanced vesiculogenesis observed in virR mutants.
Main Methods:
- Genetic analysis
- Transcriptional profiling
- Proteomics
- Ultrastructural examination
- Biochemical assays
Main Results:
- VirR is crucial for maintaining Mtb cell envelope integrity and permeability.
- VirR likely regulates cell envelope remodeling, potentially through interactions with cell wall proteins.
- These interactions influence the linkage between peptidoglycan and arabinogalactan.
Conclusions:
- VirR plays a critical role in mycobacterial extracellular vesicle biogenesis.
- VirR's function in cell envelope regulation is key to controlling EV production.
- Proteins involved in VirR-mediated pathways represent potential therapeutic targets for tuberculosis.
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