Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026
Virulence mechanisms of Desulfovibrio bacteria: viability-dependent processes promote alpha-synuclein aggregation and toxicity in C. elegans.
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Huynh Vy A, Chi Fang, Talebzadeh Sima, Hakovirta Janetta R, Simojoki Asko, Saris Per Erik Joakim
Аннотация
OBJECTIVES: Desulfovibrio (DSV) species have been linked to Parkinson's disease (PD) and demonstrated to enhance alpha-synuclein (alpha-syn) aggregation, a pathological hallmark of PD, in a Caenorhabditis elegans model. However, the bacterial factors underlying this virulence remain unclear. We investigated whether DSV-induced alpha-syn aggregation and toxicity are more strongly driven by bacterial viability-dependent processes or by bacterial structures retained after paraformaldehyde (PFA) treatment.
METHODS: Live or paraformaldehyde (PFA)-treated (non-viable) DSV cells, and curli-producing or curli-deficient E. coli as controls were fed to C. elegans. Worm survival, alpha-syn aggregation, hydrogen sulfide production, and expression of genes associated with inflammation, oxidative stress, proteostasis and dopaminergic function were evaluated.
RESULTS: Curli-producing E. coli retained its ability to induce alpha-syn aggregation, whereas PFA-treated DSV strains lost this effect, showing reduced aggregate number and volume (P < 0.05). Worm survival improved when fed PFA-treated cells, although the difference was not statistically significant. Expression of pmk-1, skn-1 and hsf-1 did not differ between worms fed live and PFA-treated DSV bacteria, while cat-2 expression increased in worms fed PFA-treated bacteria compared to those fed live cells. Patient-derived DSV strains produced substantially higher levels of H2S than healthy control strains (1058.11 vs. 710.30 ppm/OD600; P = 0.003), and H2S levels were positively correlated with aggregate volume (Spearman's rs = 0.886, P = 0.019).
CONCLUSIONS: DSV-derived viability-dependent processes, including metabolic activity, more strongly promote alpha-syn aggregation and toxicity than structural components. These findings highlight the important contribution of bacterial viability-dependent processes to DSV-mediated pathogenic effects relevant to Parkinson's disease.
METHODS: Live or paraformaldehyde (PFA)-treated (non-viable) DSV cells, and curli-producing or curli-deficient E. coli as controls were fed to C. elegans. Worm survival, alpha-syn aggregation, hydrogen sulfide production, and expression of genes associated with inflammation, oxidative stress, proteostasis and dopaminergic function were evaluated.
RESULTS: Curli-producing E. coli retained its ability to induce alpha-syn aggregation, whereas PFA-treated DSV strains lost this effect, showing reduced aggregate number and volume (P < 0.05). Worm survival improved when fed PFA-treated cells, although the difference was not statistically significant. Expression of pmk-1, skn-1 and hsf-1 did not differ between worms fed live and PFA-treated DSV bacteria, while cat-2 expression increased in worms fed PFA-treated bacteria compared to those fed live cells. Patient-derived DSV strains produced substantially higher levels of H2S than healthy control strains (1058.11 vs. 710.30 ppm/OD600; P = 0.003), and H2S levels were positively correlated with aggregate volume (Spearman's rs = 0.886, P = 0.019).
CONCLUSIONS: DSV-derived viability-dependent processes, including metabolic activity, more strongly promote alpha-syn aggregation and toxicity than structural components. These findings highlight the important contribution of bacterial viability-dependent processes to DSV-mediated pathogenic effects relevant to Parkinson's disease.