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Updated: May 11, 2025
Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
The Rough Morphotype of Mycobacterium abscessus Enhances Its Virulence Through ROS/p65/NLRP3/GSDMD-Mediated
Jingren Li1,2, Juan Li1,2, Anqi Li1,2
1Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Abstract:
The rough morphotype of Mycobacterium abscessus exhibits significantly higher virulence compared to the smooth morphotype, yet the underlying molecular mechanisms remain incompletely understood. Pyroptosis in macrophages plays a pivotal role in lung tissue damage; however, its specific involvement in Mycobacterium abscessus infection remains to be fully clarified. In this study, we identified that the rough morphotype of Mycobacterium abscessus upregulates the ROS/p65/NLRP3/GSDMD signalling pathway, thereby mediating pyroptosis in THP-1-derived macrophages. This heightened ability to induce macrophage pyroptosis is attributed to the bacterium's capacity to sustain intracellular viability and proliferation. These findings offer valuable insights into the virulence mechanisms of Mycobacterium abscessus and provide a foundation for future therapeutic interventions.
Insights
The rough Mycobacterium abscessus form triggers cell death (pyroptosis) in immune cells by activating the ROS/p65/NLRP3/GSDMD pathway. This enhanced pyroptosis contributes to the bacterium
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Mycobacterium abscessus exhibits distinct morphotypes (rough and smooth) with differing virulence.
- Macrophage pyroptosis is implicated in lung inflammation and tissue damage.
- The precise role of pyroptosis in M. abscessus infection requires further elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms by which the rough morphotype of M. abscessus induces macrophage pyroptosis.
- To identify the specific signaling pathway involved in M. abscessus-mediated pyroptosis.
Main Methods:
- Utilized THP-1-derived macrophages as a model system.
- Investigated the activation of the ROS/p65/NLRP3/GSDMD signaling pathway.
- Assessed intracellular viability and proliferation of M. abscessus.
Main Results:
- The rough morphotype of M. abscessus significantly upregulates the ROS/p65/NLRP3/GSDMD signaling pathway.
- This pathway activation leads to pyroptosis in THP-1-derived macrophages.
- The bacterium's enhanced intracellular survival and proliferation correlate with its ability to induce pyroptosis.
Conclusions:
- The rough M. abscessus morphotype utilizes the ROS/p65/NLRP3/GSDMD pathway to induce macrophage pyroptosis.
- Sustained intracellular viability and proliferation are key factors in the bacterium's virulence.
- These findings provide crucial insights into M. abscessus pathogenesis and potential therapeutic targets.
