The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation
Abstract
:1. Introduction
2. Results
2.1. Phenol Soluble Modulins Catalyze α-Syn Aggregation
2.2. PSMα Modulation of α-Syn Aggregation Is DMSO Independent
2.3. PSMα Peptides Modulate α-Syn Aggregation Differently
2.4. Composition of Aggregated Species
2.5. PSMα Peptides Induce α-Syn Aggregation by Heterogeneous Primary Nucleation
2.6. α-Syn Concentration Dependence Varies for Different PSMα Peptides
2.7. PSMα Peptides Induce α-Syn Fibril Formation
2.8. PSMα-Peptide-Induced-α-Syn Aggregates Seed α-Syn in Cells
3. Discussion
4. Materials and Methods
4.1. α-Syn Production and Purification
4.2. PSMα Production
4.3. Aggregation Kinetics Experiments
4.4. Kinetics Analysis
4.5. Electrophoresis and Mass Spectrometry
4.6. Peptide Array
4.7. Electron Microscopy
4.8. HEK 293T Culture
4.9. Phospho-α-Syn Staining of HEK 293T Cells
4.10. Quantification of Aggregates
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Braak, H.; Rub, U.; Gai, W.P.; Del Tredici, K. Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm. 2003, 110, 517–536. [Google Scholar] [CrossRef] [PubMed]
- Hawkes, C.H.; Del Tredici, K.; Braak, H. Parkinson’s disease: A dual-hit hypothesis. Neuropathol. Appl. Neurobiol. 2007, 33, 599–614. [Google Scholar] [CrossRef]
- Holmqvist, S.; Chutna, O.; Bousset, L.; Aldrin-Kirk, P.; Li, W.; Bjorklund, T.; Wang, Z.Y.; Roybon, L.; Melki, R.; Li, J.Y. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014, 128, 805–820. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, S.; Kwon, S.H.; Kam, T.I.; Panicker, N.; Karuppagounder, S.S.; Lee, S.; Lee, J.H.; Kim, W.R.; Kook, M.; Foss, C.A.; et al. Transneuronal Propagation of Pathologic alpha-Synuclein from the Gut to the Brain Models Parkinson’s Disease. Neuron 2019, 103, 627–641. [Google Scholar] [CrossRef]
- Wang, X.J.; Ma, M.M.; Zhou, L.B.; Jiang, X.Y.; Hao, M.M.; Teng, R.K.F.; Wu, E.; Tang, B.S.; Li, J.Y.; Teng, J.F.; et al. Autonomic ganglionic injection of alpha-synuclein fibrils as a model of pure autonomic failure alpha-synucleinopathy. Nat. Commun. 2020, 11, 934. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lohmann, S.; Bernis, M.E.; Tachu, B.J.; Ziemski, A.; Grigoletto, J.; Tamguney, G. Oral and intravenous transmission of alpha-synuclein fibrils to mice. Acta Neuropathol. 2019, 138, 515–533. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rey, N.L.; George, S.; Steiner, J.A.; Madaj, Z.; Luk, K.C.; Trojanowski, J.Q.; Lee, V.M.; Brundin, P. Spread of aggregates after olfactory bulb injection of alpha-synuclein fibrils is associated with early neuronal loss and is reduced long term. Acta Neuropathol. 2018, 135, 65–83. [Google Scholar] [CrossRef] [Green Version]
- Rey, N.L.; Petit, G.H.; Bousset, L.; Melki, R.; Brundin, P. Transfer of human alpha-synuclein from the olfactory bulb to interconnected brain regions in mice. Acta Neuropathol. 2013, 126, 555–573. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rey, N.L.; Steiner, J.A.; Maroof, N.; Luk, K.C.; Madaj, Z.; Trojanowski, J.Q.; Lee, V.M.; Brundin, P. Widespread transneuronal propagation of alpha-synucleinopathy triggered in olfactory bulb mimics prodromal Parkinson’s disease. J. Exp. Med. 2016, 213, 1759–1778. [Google Scholar] [CrossRef]
- Bhattacharyya, D.; Mohite, G.M.; Krishnamoorthy, J.; Gayen, N.; Mehra, S.; Navalkar, A.; Kotler, S.A.; Ratha, B.N.; Ghosh, A.; Kumar, R.; et al. Lipopolysaccharide from Gut Microbiota Modulates alpha-Synuclein Aggregation and Alters Its Biological Function. ACS Chem. Neurosci. 2019, 10, 2229–2236. [Google Scholar] [CrossRef]
- Chorell, E.; Andersson, E.; Evans, M.L.; Jain, N.; Gotheson, A.; Aden, J.; Chapman, M.R.; Almqvist, F.; Wittung-Stafshede, P. Bacterial Chaperones CsgE and CsgC Differentially Modulate Human alpha-Synuclein Amyloid Formation via Transient Contacts. PLoS ONE 2015, 10, e0140194. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, C.; Lv, G.; Lee, J.S.; Jung, B.C.; Masuda-Suzukake, M.; Hong, C.S.; Valera, E.; Lee, H.J.; Paik, S.R.; Hasegawa, M.; et al. Exposure to bacterial endotoxin generates a distinct strain of alpha-synuclein fibril. Sci. Rep. 2016, 6, 30891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guo, J.L.; Covell, D.J.; Daniels, J.P.; Iba, M.; Stieber, A.; Zhang, B.; Riddle, D.M.; Kwong, L.K.; Xu, Y.; Trojanowski, J.Q.; et al. Distinct alpha-synuclein strains differentially promote tau inclusions in neurons. Cell 2013, 154, 103–117. [Google Scholar] [CrossRef] [Green Version]
- Chia, S.; Flagmeier, P.; Habchi, J.; Lattanzi, V.; Linse, S.; Dobson, C.M.; Knowles, T.P.J.; Vendruscolo, M. Monomeric and fibrillar alpha-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Abeta42 aggregates. Proc. Natl. Acad. Sci. USA 2017, 114, 8005–8010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, S.G.; Stribinskis, V.; Rane, M.J.; Demuth, D.R.; Gozal, E.; Roberts, A.M.; Jagadapillai, R.; Liu, R.; Choe, K.; Shivakumar, B.; et al. Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans. Sci. Rep. 2016, 6, 34477. [Google Scholar] [CrossRef]
- Romero, D.; Kolter, R. Functional amyloids in bacteria. Int. Microbiol. 2014, 17, 65–73. [Google Scholar] [CrossRef] [PubMed]
- Benfield, T.; Espersen, F.; Frimodt-Moller, N.; Jensen, A.G.; Larsen, A.R.; Pallesen, L.V.; Skov, R.; Westh, H.; Skinhoj, P. Increasing incidence but decreasing in-hospital mortality of adult Staphylococcus aureus bacteraemia between 1981 and 2000. Clin. Microbiol. Infect. 2007, 13, 257–263. [Google Scholar] [CrossRef] [Green Version]
- Acton, D.S.; Plat-Sinnige, M.J.; van Wamel, W.; de Groot, N.; van Belkum, A. Intestinal carriage of Staphylococcus aureus: How does its frequency compare with that of nasal carriage and what is its clinical impact? Eur. J. Clin. Microbiol. Infect. Dis. 2009, 28, 115–127. [Google Scholar] [CrossRef] [Green Version]
- Dong, D.; Ni, Q.; Wang, C.; Zhang, L.; Li, Z.; Jiang, C.; Peng, Y. Effects of intestinal colonization by Clostridium difficile and Staphylococcus aureus on microbiota diversity in healthy individuals in China. BMC Infect. Dis. 2018, 18, 207. [Google Scholar] [CrossRef] [PubMed]
- Kates, A.E.; Thapaliya, D.; Smith, T.C.; Chorazy, M.L. Prevalence and molecular characterization of Staphylococcus aureus from human stool samples. Antimicrob. Resist. Infect. Control 2018, 7, 42. [Google Scholar] [CrossRef] [Green Version]
- Kluytmans, J.; van Belkum, A.; Verbrugh, H. Nasal carriage of Staphylococcus aureus: Epidemiology, underlying mechanisms, and associated risks. Clin. Microbiol. Rev. 1997, 10, 505–520. [Google Scholar] [CrossRef] [PubMed]
- Najarzadeh, Z.; Zaman, M.; Sereikaite, V.; Stromgaard, K.; Andreasen, M.; Otzen, D.E. Heparin promotes fibrillation of most phenol soluble modulin virulence peptides from S. aureus. J. Biol. Chem. 2021, 100953. [Google Scholar] [CrossRef] [PubMed]
- Wang, R.; Braughton, K.R.; Kretschmer, D.; Bach, T.H.; Queck, S.Y.; Li, M.; Kennedy, A.D.; Dorward, D.W.; Klebanoff, S.J.; Peschel, A.; et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat. Med. 2007, 13, 1510–1514. [Google Scholar] [CrossRef] [PubMed]
- Bjornsdottir, H.; Dahlstrand Rudin, A.; Klose, F.P.; Elmwall, J.; Welin, A.; Stylianou, M.; Christenson, K.; Urban, C.F.; Forsman, H.; Dahlgren, C.; et al. Phenol-Soluble Modulin alpha Peptide Toxins from Aggressive Staphylococcus aureus Induce Rapid Formation of Neutrophil Extracellular Traps through a Reactive Oxygen Species-Independent Pathway. Front. Immunol. 2017, 8, 257. [Google Scholar] [CrossRef] [Green Version]
- Greenlee-Wacker, M.; DeLeo, F.R.; Nauseef, W.M. How methicillin-resistant Staphylococcus aureus evade neutrophil killing. Curr. Opin. Hematol. 2015, 22, 30–35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McGuinness, W.A.; Kobayashi, S.D.; DeLeo, F.R. Evasion of Neutrophil Killing by Staphylococcus aureus. Pathogens 2016, 5, 32. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Azevedo, E.P.; Guimaraes-Costa, A.B.; Torezani, G.S.; Braga, C.A.; Palhano, F.L.; Kelly, J.W.; Saraiva, E.M.; Foguel, D. Amyloid fibrils trigger the release of neutrophil extracellular traps (NETs), causing fibril fragmentation by NET-associated elastase. J. Biol. Chem. 2012, 287, 37206–37218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chiu, I.M.; Heesters, B.A.; Ghasemlou, N.; Von Hehn, C.A.; Zhao, F.; Tran, J.; Wainger, B.; Strominger, A.; Muralidharan, S.; Horswill, A.R.; et al. Bacteria activate sensory neurons that modulate pain and inflammation. Nature 2013, 501, 52–57. [Google Scholar] [CrossRef] [Green Version]
- Blake, K.J.; Baral, P.; Voisin, T.; Lubkin, A.; Pinho-Ribeiro, F.A.; Adams, K.L.; Roberson, D.P.; Ma, Y.C.; Otto, M.; Woolf, C.J.; et al. Staphylococcus aureus produces pain through pore-forming toxins and neuronal TRPV1 that is silenced by QX-314. Nat. Commun. 2018, 9, 37. [Google Scholar] [CrossRef] [PubMed]
- Uhlig, F.; Grundy, L.; Garcia-Caraballo, S.; Brierley, S.M.; Foster, S.J.; Grundy, D. Identification of a Quorum Sensing-Dependent Communication Pathway Mediating Bacteria-Gut-Brain Cross Talk. iScience 2020, 23, 101695. [Google Scholar] [CrossRef]
- Valek, L.; Auburger, G.; Tegeder, I. Sensory neuropathy and nociception in rodent models of Parkinson’s disease. Dis. Model. Mech. 2019, 12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Braak, H.; Sastre, M.; Bohl, J.R.; de Vos, R.A.; Del Tredici, K. Parkinson’s disease: Lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons. Acta Neuropathol. 2007, 113, 421–429. [Google Scholar] [CrossRef] [PubMed]
- Beach, T.G.; Adler, C.H.; Sue, L.I.; Vedders, L.; Lue, L.; White Iii, C.L.; Akiyama, H.; Caviness, J.N.; Shill, H.A.; Sabbagh, M.N.; et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010, 119, 689–702. [Google Scholar] [CrossRef] [Green Version]
- Sumikura, H.; Takao, M.; Hatsuta, H.; Ito, S.; Nakano, Y.; Uchino, A.; Nogami, A.; Saito, Y.; Mochizuki, H.; Murayama, S. Distribution of alpha-synuclein in the spinal cord and dorsal root ganglia in an autopsy cohort of elderly persons. Acta Neuropathol. Commun. 2015, 3, 57. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marinelli, P.; Pallares, I.; Navarro, S.; Ventura, S. Dissecting the contribution of Staphylococcus aureus alpha-phenol-soluble modulins to biofilm amyloid structure. Sci. Rep. 2016, 6, 34552. [Google Scholar] [CrossRef]
- Tayeb-Fligelman, E.; Tabachnikov, O.; Moshe, A.; Goldshmidt-Tran, O.; Sawaya, M.R.; Coquelle, N.; Colletier, J.P.; Landau, M. The cytotoxic Staphylococcus aureus PSMalpha3 reveals a cross-alpha amyloid-like fibril. Science 2017, 355, 831–833. [Google Scholar] [CrossRef]
- Galvagnion, C.; Buell, A.K.; Meisl, G.; Michaels, T.C.; Vendruscolo, M.; Knowles, T.P.; Dobson, C.M. Lipid vesicles trigger alpha-synuclein aggregation by stimulating primary nucleation. Nat. Chem. Biol. 2015, 11, 229–234. [Google Scholar] [CrossRef] [Green Version]
- Habchi, J.; Chia, S.; Galvagnion, C.; Michaels, T.C.T.; Bellaiche, M.M.J.; Ruggeri, F.S.; Sanguanini, M.; Idini, I.; Kumita, J.R.; Sparr, E.; et al. Cholesterol catalyses Abeta42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes. Nat. Chem. 2018, 10, 673–683. [Google Scholar] [CrossRef]
- Cukalevski, R.; Yang, X.; Meisl, G.; Weininger, U.; Bernfur, K.; Frohm, B.; Knowles, T.P.J.; Linse, S. The Abeta40 and Abeta42 peptides self-assemble into separate homomolecular fibrils in binary mixtures but cross-react during primary nucleation. Chem. Sci. 2015, 6, 4215–4233. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Oliveira, G.A.P.; Silva, J.L. Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson’s disease. Commun. Biol. 2019, 2, 374. [Google Scholar] [CrossRef] [Green Version]
- Arosio, P.; Cukalevski, R.; Frohm, B.; Knowles, T.P.; Linse, S. Quantification of the concentration of Abeta42 propagons during the lag phase by an amyloid chain reaction assay. J. Am. Chem. Soc. 2014, 136, 219–225. [Google Scholar] [CrossRef] [PubMed]
- Arosio, P.; Knowles, T.P.; Linse, S. On the lag phase in amyloid fibril formation. Phys. Chem. Chem. Phys. 2015, 17, 7606–7618. [Google Scholar] [CrossRef] [Green Version]
- Svanbergsson, A.; Ek, F.; Martinsson, I.; Rodo, J.; Liu, D.; Brandi, E.; Haikal, C.; Torres-Garcia, L.; Li, W.; Gouras, G.; et al. FRET-Based Screening Identifies p38 MAPK and PKC Inhibition as Targets for Prevention of Seeded alpha-Synuclein Aggregation. Neurotherapeutics 2021. [Google Scholar] [CrossRef]
- Linse, S. Monomer-dependent secondary nucleation in amyloid formation. Biophys. Rev. 2017, 9, 329–338. [Google Scholar] [CrossRef] [Green Version]
- Buell, A.K.; Galvagnion, C.; Gaspar, R.; Sparr, E.; Vendruscolo, M.; Knowles, T.P.; Linse, S.; Dobson, C.M. Solution conditions determine the relative importance of nucleation and growth processes in alpha-synuclein aggregation. Proc. Natl. Acad. Sci. USA 2014, 111, 7671–7676. [Google Scholar] [CrossRef] [Green Version]
- Vacha, R.; Linse, S.; Lund, M. Surface effects on aggregation kinetics of amyloidogenic peptides. J. Am. Chem. Soc. 2014, 136, 11776–11782. [Google Scholar] [CrossRef] [PubMed]
- Campioni, S.; Carret, G.; Jordens, S.; Nicoud, L.; Mezzenga, R.; Riek, R. The presence of an air-water interface affects formation and elongation of alpha-Synuclein fibrils. J. Am. Chem. Soc. 2014, 136, 2866–2875. [Google Scholar] [CrossRef]
- Gaspar, R.; Lund, M.; Sparr, E.; Linse, S. Anomalous Salt Dependence Reveals an Interplay of Attractive and Repulsive Electrostatic Interactions in α-synuclein Fibril Formation. QRB Discov. 2020, 1, e2. [Google Scholar] [CrossRef]
- Zaman, M.; Andreasen, M. Modulating Kinetics of the Amyloid-Like Aggregation of S. aureus Phenol-Soluble Modulins by Changes in pH. Microorganisms 2021, 9, 117. [Google Scholar] [CrossRef]
- Krismer, B.; Peschel, A. Does Staphylococcus aureus nasal colonization involve biofilm formation? Future Microbiol. 2011, 6, 489–493. [Google Scholar] [CrossRef] [PubMed]
- Grey, M.; Linse, S.; Nilsson, H.; Brundin, P.; Sparr, E. Membrane interaction of alpha-synuclein in different aggregation states. J. Parkinson’s Dis. 2011, 1, 359–371. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meisl, G.; Kirkegaard, J.B.; Arosio, P.; Michaels, T.C.; Vendruscolo, M.; Dobson, C.M.; Linse, S.; Knowles, T.P. Molecular mechanisms of protein aggregation from global fitting of kinetic models. Nat. Protoc. 2016, 11, 252–272. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Haikal, C.; Ortigosa-Pascual, L.; Najarzadeh, Z.; Bernfur, K.; Svanbergsson, A.; Otzen, D.E.; Linse, S.; Li, J.-Y. The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation. Int. J. Mol. Sci. 2021, 22, 11594. https://doi.org/10.3390/ijms222111594
Haikal C, Ortigosa-Pascual L, Najarzadeh Z, Bernfur K, Svanbergsson A, Otzen DE, Linse S, Li J-Y. The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation. International Journal of Molecular Sciences. 2021; 22(21):11594. https://doi.org/10.3390/ijms222111594
Chicago/Turabian StyleHaikal, Caroline, Lei Ortigosa-Pascual, Zahra Najarzadeh, Katja Bernfur, Alexander Svanbergsson, Daniel E. Otzen, Sara Linse, and Jia-Yi Li. 2021. "The Bacterial Amyloids Phenol Soluble Modulins from Staphylococcus aureus Catalyze Alpha-Synuclein Aggregation" International Journal of Molecular Sciences 22, no. 21: 11594. https://doi.org/10.3390/ijms222111594