The bacterial amyloids phenol soluble modulins from staphylococcus aureus catalyze alpha-synuclein aggregation
Haikal, Caroline LU ; Pascual, Lei Ortigosa LU ; Najarzadeh, Zahra ; Bernfur, Katja LU ; Svanbergsson, Alexander LU
; Otzen, Daniel E.
; Linse, Sara
LU
and Li, Jia Yi
LU
(2021)
In International Journal of Molecular Sciences
22(21).
- Abstract
Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, which are a 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 of the microbiome in the initiation of pathology of PD. Staphylococcus aureus is a bacterium carried by 30–70% of the general population. It has been shown to produce functional amy-loids, called phenol soluble modulins (PSMαs). Here, we studied the kinetics of α-syn aggregation under quiescent conditions in the presence or absence of four... (More)
Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, which are a 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 of the microbiome in the initiation of pathology of PD. Staphylococcus aureus is a bacterium carried by 30–70% of the general population. It has been shown to produce functional amy-loids, 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 all four peptides catalyze α-syn aggregation through heterogeneous primary nucleation. The immunogold electron microscopic analyses showed that the aggregates were fibrillar and composed of α-syn. In addition of the co-aggregated materials to a cell model 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.
(Less)
- author
- Haikal, Caroline
LU
; Pascual, Lei Ortigosa
LU
; Najarzadeh, Zahra
; Bernfur, Katja
LU
; Svanbergsson, Alexander
LU
; Otzen, Daniel E.
; Linse, Sara
LU
and Li, Jia Yi
LU
- organization
- publishing date
- 2021-11-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aggregation, Alpha-synuclein, Bacterial amyloids, Parkinson’s disease, Protein folding
- in
- International Journal of Molecular Sciences
- volume
- 22
- issue
- 21
- article number
- 11594
- publisher
- MDPI AG
- external identifiers
-
- pmid:34769023
- scopus:85117928681
- ISSN
- 1661-6596
- DOI
- 10.3390/ijms222111594
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- id
- 3e75e986-b09e-4f4e-9054-1ac20df8a330
- date added to LUP
- 2021-11-22 13:59:47
- date last changed
- 2024-04-06 13:45:17
@article{3e75e986-b09e-4f4e-9054-1ac20df8a330,
abstract = {{<p>Aggregated α-synuclein (α-syn) is the main constituent of Lewy bodies, which are a 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 of the microbiome in the initiation of pathology of PD. Staphylococcus aureus is a bacterium carried by 30–70% of the general population. It has been shown to produce functional amy-loids, 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 all four peptides catalyze α-syn aggregation through heterogeneous primary nucleation. The immunogold electron microscopic analyses showed that the aggregates were fibrillar and composed of α-syn. In addition of the co-aggregated materials to a cell model 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.</p>}},
author = {{Haikal, Caroline and Pascual, Lei Ortigosa and Najarzadeh, Zahra and Bernfur, Katja and Svanbergsson, Alexander and Otzen, Daniel E. and Linse, Sara and Li, Jia Yi}},
issn = {{1661-6596}},
keywords = {{Aggregation; Alpha-synuclein; Bacterial amyloids; Parkinson’s disease; Protein folding}},
language = {{eng}},
month = {{11}},
number = {{21}},
publisher = {{MDPI AG}},
series = {{International Journal of Molecular Sciences}},
title = {{The bacterial amyloids phenol soluble modulins from staphylococcus aureus catalyze alpha-synuclein aggregation}},
url = {{http://dx.doi.org/10.3390/ijms222111594}},
doi = {{10.3390/ijms222111594}},
volume = {{22}},
year = {{2021}},
}