Salmonella Typhimurium disrupts Sirt1/AMPK checkpoint control of mTOR to impair autophagy.
Level 5 - mechanism / opinion, no new human data
In vitro mechanistic bench research with no human clinical data.
PubMed 28192515 · doi:10.1371/journal.ppat.1006227
What was done
The authors investigated how intracellular *Salmonella* Typhimurium alters host cell energy-sensing pathways to evade autophagy. They characterized the interaction and activation of Sirt1, LKB1, and AMPK upstream of mTOR, and compared host pathway degradation during infection with wild-type *S.* Typhimurium versus pathogenicity island 2 mutant strains (ΔssrB and ΔssaV).
What was found
The abstract reports no quantitative metrics or effect sizes. Infection caused transient activation of AMPK via a cytosolic Sirt1/LKB1 complex (where Sirt1 deacetylation activated LKB1), followed by the rapid targeting of Sirt1, LKB1, and AMPK to lysosomes for degradation. This degradation disrupted AMPK-mediated mTOR and autophagy regulation. SPI2 mutant strains (ΔssrB and ΔssaV) failed to degrade the Sirt1/LKB1/AMPK complex.
Why it matters
The findings identify a specific virulence strategy where *S.* Typhimurium selectively degrades host metabolic checkpoint proteins to suppress autophagic pathogen clearance.
Limits
The abstract contains no numerical data, sample sizes, or cellular model details. As pure in vitro mechanistic research, findings may not directly translate to in vivo infection dynamics or human disease.
Cited by
- supports Cellular deacetylation reactions trigger downstream inhibition of mTOR and activation of AMPK.