The Rough Morphotype of Mycobacterium abscessus Enhances Its Virulence Through ROS/p65/NLRP3/GSDMD-Mediated...

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.