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Updated: Jun 13, 2025
Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Characterization of Exosomes Released from Mycobacterium abscessus-Infected Macrophages
Charlie A Vermeire1,2, Xuejuan Tan1,2, Aidaly Ramos-Leyva1,2
1Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, USA.
Abstract:
Extracellular vesicles (EVs), such as exosomes, play a critical role in cell-to-cell communication and regulating cellular processes in recipient cells. Non-tuberculous mycobacteria (NTM), such as Mycobacterium abscessus, are a group of environmental bacteria that can cause severe lung infections in populations with pre-existing lung conditions, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). There is limited knowledge of the engagement of EVs in the host-pathogen interactions in the context of NTM infections. In this study, we found that M. abscessus infection increased the release of a subpopulation of exosomes (CD9, CD63, and/or CD81 positive) by mouse macrophages in cell culture. Proteomic analysis of these vesicles demonstrated that M. abscessus infection affects the enrichment of host proteins in exosomes released by macrophages. When compared to exosomes from uninfected macrophages, exosomes released by M. abscessus-infected macrophages significantly improved M. abscessus growth and downregulated the intracellular level of glutamine in recipient macrophages in cell culture. Increasing glutamine concentration in the medium rescued intracellular glutamine levels and M. abscessus killing in recipient macrophages that were treated with exosomes from M. abscessus-infected macrophages. Taken together, our results indicate that exosomes may serve as extracellular glutamine eliminators that interfere with glutamine-dependent M. abscessus killing in recipient macrophages.
Insights
Mycobacterium abscessus infection prompts macrophages to release exosomes that deplete glutamine in recipient cells, hindering bacterial killing. Restoring glutamine levels rescues this effect, revealing a novel host-pathogen interaction mechanism.
Area of Science:
- Cell Biology
- Microbiology
- Immunology
Background:
- Extracellular vesicles (EVs), including exosomes, are key mediators of intercellular communication.
- Non-tuberculous mycobacteria (NTM), like Mycobacterium abscessus, cause severe lung infections, particularly in individuals with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD).
- The role of EVs in host-pathogen interactions during NTM infections remains largely unexplored.
Purpose of the Study:
- To investigate the role of exosomes released by macrophages during Mycobacterium abscessus infection.
- To determine how these exosomes influence host-pathogen dynamics and bacterial growth.
- To elucidate the underlying molecular mechanisms, focusing on nutrient availability.
Main Methods:
- Macrophage cell cultures were infected with Mycobacterium abscessus.
- Exosomes released by infected and uninfected macrophages were isolated and characterized.
- Proteomic analysis was performed on isolated exosomes.
- The impact of exosomes on recipient macrophages and M. abscessus growth was assessed.
- Glutamine levels in recipient macrophages were measured and manipulated.
Main Results:
- Mycobacterium abscessus infection stimulated the release of specific exosome subpopulations (CD9, CD63, CD81 positive) from mouse macrophages.
- Proteomic analysis revealed altered host protein enrichment in exosomes from infected macrophages.
- Exosomes from M. abscessus-infected macrophages promoted bacterial growth and reduced intracellular glutamine levels in recipient macrophages.
- Supplementation of glutamine in the culture medium reversed the exosome-mediated effects, restoring glutamine levels and enhancing M. abscessus killing.
Conclusions:
- Exosomes released by M. abscessus-infected macrophages act as extracellular glutamine scavengers.
- This exosome-mediated glutamine depletion impairs the host's ability to kill M. abscessus within recipient macrophages.
- These findings uncover a novel mechanism by which NTM evades host immunity through exosome-mediated nutrient manipulation.
