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Identification of Virulence Markers of Mycobacterium abscessus for Intracellular Replication in Phagocytes
Published on: September 27, 2018
Human pluripotent stem cell-derived macrophages host Mycobacterium abscessus infection
Shicheng Sun1, Michael See2, Hieu T Nim3
1Murdoch Children's Research Institute, The Royal Children's Hospital, Flemington Road, Parkville, VIC 3052, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC 3052, Australia; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children's Research Institute, Parkville, VIC, Australia.
Researchers developed a new human stem cell-derived macrophage model for studying Mycobacterium abscessus infections. This breakthrough offers a reliable system for understanding pathogen-host interactions and discovering new treatments.
Area of Science:
- Infectious Diseases
- Cell Biology
- Drug Discovery
Background:
- Mycobacterium abscessus (M. abscessus) is an emerging pathogen infecting immunocompromised and cystic fibrosis patients.
- Effective treatments are limited due to a lack of suitable in vitro intracellular infection models.
- Human macrophages are natural hosts for mycobacteria.
Purpose of the Study:
- To establish a reliable human pluripotent stem cell-derived macrophage (hPSC-macrophage) model for M. abscessus infection.
- To enable the study of M. abscessus-host interactions.
- To facilitate drug discovery for M. abscessus infections.
Main Methods:
- Generation of functional hPSC-macrophages from human pluripotent stem cells.
- Infection of hPSC-macrophages with M. abscessus.
- Electron microscopy to visualize intracellular bacteria.
- RNA sequencing to analyze host cell response.
- Development of engineered hPSC-macrophages for high-throughput analysis.
Main Results:
- hPSC-macrophages were highly susceptible to M. abscessus infection.
- M. abscessus was observed within hPSC-macrophage vacuoles.
- Time-dependent host cell gene and protein expression changes were identified post-infection.
- Engineered macrophages enabled rapid image-based analysis and antibiotic efficacy assessment.
Conclusions:
- The study presents the first hPSC-based model for M. abscessus infection.
- This novel model provides an accessible system for studying M. abscessus pathogenesis.
- The model is valuable for drug discovery and development against M. abscessus.

