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The bacterial amyloids phenol soluble modulins from Staphylococcus aureus catalyze alpha-synuclein aggregation

Caroline Haikal, Lei Ortigosa, Katja Bernfur, View ORCID ProfileAlexander Svanbergsson, Sara Linse, Jia-Yi Li
doi: https://doi.org/10.1101/2021.03.10.434765
Caroline Haikal
1Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden
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Lei Ortigosa
2Center for Molecular Protein Science, Department of Chemistry and Structural Biology, Lund University, 22241 Lund, Sweden
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Katja Bernfur
2Center for Molecular Protein Science, Department of Chemistry and Structural Biology, Lund University, 22241 Lund, Sweden
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Alexander Svanbergsson
1Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden
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  • ORCID record for Alexander Svanbergsson
Sara Linse
2Center for Molecular Protein Science, Department of Chemistry and Structural Biology, Lund University, 22241 Lund, Sweden
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Jia-Yi Li
1Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, 22184 Lund, Sweden
3Institute of Health Sciences, China Medical University, Shenyang 110112, China
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  • For correspondence: jia-yi.li@med.lu.se
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Abstract

Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, the main pathological hallmark of Parkinson’s disease (PD). Environmental factors are thought to be potential triggers capable of initiating the aggregation of the otherwise monomeric α-syn. Braak’s seminal work redirected attention to the intestine and recent reports of dysbiosis have highlighted the potential causative role that the microbiome might play in the pathology of PD. Staphylococcus aureus is a bacterium carried by 30-70% of the general population. It has been shown to produce functional amyloids, called Phenol Soluble Modulins (PSMαs). Here, we studied the kinetics of α-syn aggregation under quiescent conditions in the presence or absence of four different PSMα peptides and observed a remarkable shortening of the lag phase in their presence. Whereas pure α-syn monomer did not aggregate up to 450 h after initiation of the experiment in neither neutral nor mildly acidic buffer, the addition of different PSMα peptides resulted in an almost immediate increase in the Thioflavin T (ThT) fluorescence. Despite similar peptide sequences, the different PSMα peptides displayed distinct effects on the kinetics of α-syn aggregation. Kinetic analyses of the data suggest that while all four peptides catalyze α-syn aggregation, the underlying mechanisms might differ with a model of nucleation and elongation fitting the α-syn aggregation induced by PSMα2 but not PSMα1. The results of immunogold TEM imply that the aggregates are fibrillar and composed of α-syn. Addition of the co-aggregated materials to HEK cells expressing the A53T α-syn variant fused to GFP was found to catalyze α-syn aggregation and phosphorylation in the cells. Our results provide evidence of a potential trigger of synucleinopathies and could have implications for the prevention of the diseases.

Competing Interest Statement

The authors have declared no competing interest.

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Posted March 10, 2021.
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The bacterial amyloids phenol soluble modulins from Staphylococcus aureus catalyze alpha-synuclein aggregation
Caroline Haikal, Lei Ortigosa, Katja Bernfur, Alexander Svanbergsson, Sara Linse, Jia-Yi Li
bioRxiv 2021.03.10.434765; doi: https://doi.org/10.1101/2021.03.10.434765
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The bacterial amyloids phenol soluble modulins from Staphylococcus aureus catalyze alpha-synuclein aggregation
Caroline Haikal, Lei Ortigosa, Katja Bernfur, Alexander Svanbergsson, Sara Linse, Jia-Yi Li
bioRxiv 2021.03.10.434765; doi: https://doi.org/10.1101/2021.03.10.434765

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