Authors:

Yoan Argote

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About Paper:

The sporadic onset of 90% of neurodegenerative Protein Conformational Disease (PCD) cases underscores the need to identify factors involved in disease pathogenesis. A growing body o f literature has established a correlation between gut dysbiosis and PCDs. Recent work in o ur laboratory has identified the impact of 229 human bacterial isolates on PCD-associated prote ins using Caenorhabditis elegans expressing polyglutamine, Aβ1-42, tau, and α-synuclein. We have determined that toxic protein aggregation is robustly suppressed by Prevotella corporis, regardless of the disease-associated protein in the host, suggesting an upstream bacterial effect on host proteostasis. These findings are consistent with literature that associates a depletion in the Prevotella genus with increased PCD occurrence and severity. Here, we elucidate the mechanistic basis of the observed proteoprotective effect that P. corporis has a on the host, specifically the effects this bacterium uniquely exerts on the heat shock response (HSR) and oxidative stress response (OSR), the interactions between these pathways, and their resulting effects on toxic protein aggregation in the host. Using C. elegans expressing hsp70p::GFP as a readout for the HSR and DAF-16::GFP for the OSR, we found that P. corporis not only induces the HSR but also the disaggregation of polyglutamine aggregates, providing mechanistic insights into how this proteoprotective bacterium affects host proteostasis. Our findings suggest a role for bacteria in the sporadic development of PCDs by affecting host stress responses and altering the host's transcriptome, galvanizing a novel microbial approach for managing neurodegenerative disease. Prevotella corporis Prevents and Reverses Protein Aggregation in Caenorhabditis

Source:

University of Florida / Yoan Argote, Alyssa Walker, Daniel Czyz / 2024

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Co-authors:

Yoan Argote