Salgueiro-Toledo, V.C., Bertol, J., Gutierrez, C. orcid.org/0000-0003-1777-0223 et al. (19 more authors) (2025) Maintenance of cell wall remodeling and vesicle production are connected in Mycobacterium tuberculosis. eLife, 13. RP94982. ISSN 2050-084X
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 (virRmut) 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 virRmut. 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Mycobacterium tuberculosis; biogenesis; cell wall; extracellular vesicles; infectious disease; microbiology; mycobacterium tuberculosis; Mycobacterium tuberculosis; Cell Wall; Extracellular Vesicles; Bacterial Proteins; Animals; Proteomics; Mice |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Physics and Astronomy (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 24 Feb 2025 10:50 |
Last Modified: | 24 Feb 2025 10:50 |
Published Version: | https://doi.org/10.7554/elife.94982 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.94982 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:223682 |