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Published on: July 27, 2018
Induction of autophagy by anthrax lethal toxin
Yian Kim Tan1, Caroline M Kusuma, Lena J St John
1Molecular and Microbiology Department, College of Sciences, George Mason University, Manassas, VA 22010, USA.
Anthrax lethal toxin (LT) triggers autophagy, a cellular self-cleaning process, in mammalian cells. Inhibiting this autophagy accelerates cell death, suggesting a protective role in anthrax intoxication.
Area of Science:
- Cell Biology
- Immunology
- Microbiology
Background:
- Autophagy is a fundamental cellular process for degrading damaged proteins and organelles.
- Increasing evidence highlights autophagy's role in the pathogenesis of infectious diseases.
- Anthrax lethal toxin (LT) significantly impacts cellular functions.
Purpose of the Study:
- To investigate the novel effect of anthrax lethal toxin (LT) on inducing autophagy in mammalian cells.
- To elucidate the specific components of LT responsible for triggering autophagy.
- To explore the potential protective role of autophagy in LT intoxication.
Main Methods:
- Treatment of mammalian cells with anthrax lethal toxin (LT) and its components.
- Monitoring of autophagy markers: LC3-II conversion, GFP-LC3 punctuate distribution, and acidic vesicular organelles (AVO) formation.
- Assessment of cell viability following autophagy inhibition in the presence of LT.
Main Results:
- LT treatment induced significant autophagy, evidenced by increased LC3-II conversion, GFP-LC3 puncta, and AVO development.
- The protective antigen component of LT moderately increased LC3-II conversion; lethal factor had no effect.
- Inhibition of autophagy led to accelerated cell death, indicating a protective function.
Conclusions:
- Anthrax lethal toxin (LT) induces autophagy in mammalian cells through a mechanism not solely dependent on lethal factor.
- Autophagy appears to play a protective role against LT-induced cellular damage.
- This study lays the foundation for further research into autophagy's involvement in anthrax pathogenesis.
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