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Project Title
Influence of age-derived dental collagen glycation on bacterial adhesion and initial biofilm formation of oral streptococci
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Internal ID
11180101
Principal Investigator
Sebastian Aguayo
Start Date
2018

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Nanoscale Dynamics of Streptococcal Adhesion to AGE-Modified Collagen

2023 , C. Leiva-Sabadini , P. Tiozzo-Lyon , L. Hidalgo-Galleguillos , L. Rivas , A.I. Robles , A. Fierro , N.P. Barrera , L. Bozec , C.M.A.P. Schuh , S. Aguayo

The adhesion of initial colonizers such as Streptococcus mutans to collagen is critical for dentinal and root caries progression. One of the most described pathological and aging-associated changes in collagen—including dentinal collagen—is the generation of advanced glycation end-products (AGEs) such as methylglyoxal (MGO)–derived AGEs. Despite previous reports suggesting that AGEs alter bacterial adhesion to collagen, the biophysics driving oral streptococcal attachment to MGO-modified collagen remains largely understudied. Thus, the aim of this work was to unravel the dynamics of the initial adhesion of S. mutans to type I collagen in the presence and absence of MGO-derived AGEs by employing bacterial cell force spectroscopy with atomic force microscopy (AFM). Type I collagen gels were treated with 10 mM MGO to induce AGE formation, which was characterized with microscopy and enzyme-linked immunosorbent assay. Subsequently, AFM cantilevers were functionalized with living S. mutans UA 159 or Streptococcus sanguinis SK 36 cells and probed against collagen surfaces to obtain force curves displaying bacterial attachment in real time, from which the adhesion force, number of events, Poisson analysis, and contour and rupture lengths for each individual detachment event were computed. Furthermore, in silico computer simulation docking studies between the relevant S. mutans UA 159 collagen-binding protein SpaP and collagen were computed, in the presence and absence of MGO. Overall, results showed that MGO modification increased both the number and adhesion force of single-unbinding events between S. mutans and collagen, without altering the contour or rupture lengths. Both experimental and in silico simulations suggest that this effect is due to increased specific and nonspecific forces and interactions between S. mutans UA 159 and MGO-modified collagen substrates. In summary, these results suggest that collagen alterations due to aging and glycation may play a role in early bacterial adherence to oral tissues, associated with conditions such as aging or chronic hyperglycemia, among others.

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Nanomechanical and Molecular Characterization of Aging in Dentinal Collagen

2022 , C.M.A.P. Schuh , C. Leiva-Sabadini , S. Huang , N.P. Barrera , L. Bozec , S. Aguayo

Methylglyoxal (MGO) is an important molecule derived from glucose metabolism with the capacity of attaching to collagen and generating advanced glycation end products (AGEs), which accumulate in tissues over time and are associated with aging and diseases. However, the accumulation of MGO-derived AGEs in dentin and their effect on the nanomechanical properties of dentinal collagen remain unknown. Thus, the aim of the present study was to quantify MGO-based AGEs in the organic matrix of human dentin as a function of age and associate these changes with alterations in the nanomechanical and ultrastructural properties of dentinal collagen. For this, 12 healthy teeth from <26-y-old and >50-y-old patients were collected and prepared to obtain crown and root dentin discs. Following demineralization, MGO-derived AGEs were quantified with a competitive ELISA. In addition, atomic force microscopy nanoindentation was utilized to measure changes in elastic modulus in peritubular and intertubular collagen fibrils. Finally, principal component analysis was carried out to determine aging profiles for crown and root dentin. Results showed an increased presence of MGO AGEs in the organic matrix of dentin in the >50-y-old specimens as compared with the <26-y-old specimens in crown and root. Furthermore, an increase in peritubular and intertubular collagen elasticity was observed in the >50-y-old group associated with ultrastructural changes in the organic matrix as determined by atomic force microscopy analysis. Furthermore, principal component analysis loading plots suggested different “aging profiles” in crown and root dentin, which could have important therapeutic implications in restorative and adhesive dentistry approaches. Overall, these results demonstrate that the organic matrix of human dentin undergoes aging-related changes due to MGO-derived AGEs with important changes in the nanomechanical behavior of collagen that may affect diagnostic and restorative procedures in older people.

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Type I collagen hydrogels as a delivery matrix for royal jelly derived extracellular vesicles

2020 , Orlando J. Ramírez , Simón Alvarez , Pamina Contreras-Kallens , Nelson P. Barrera , Sebastian Aguayo , Christina M. A. P. Schuh

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Bacterial adhesion to collagens: implications for biofilm formation and disease progression in the oral cavity

2021 , Simón Álvarez , Camila Leiva-Sabadini , Christina M. A. P. Schuh , Sebastian Aguayo

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Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy

2022 , Camila Leiva‐Sabadini , Christina MAP Schuh , Nelson P. Barrera , Sebastian Aguayo

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Potential Novel Strategies for the Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and Beyond

2019 , SCHUH, CHRISTINA , Bruna Benso , Sebastian Aguayo

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Exosome-like vesicles in Apis mellifera bee pollen, honey and royal jelly contribute to their antibacterial and pro-regenerative activity

2019 , Christina M. A. P. Schuh , Sebastian Aguayo , Gabriela Zavala , Maroun Khoury

Microvesicles have become key players in cellular communication. Since glandular secretions present a rich source of active exosomes, we hypothesized that exosome-like vesicles are present in Apis mellifera hypopharyngeal gland secretomal products (honey, royal jelly and bee pollen), and participate in their known antibacterial and pro-regenerative effects. We developed an isolation protocol based on serial- and ultracentrifugation steps and demonstrated the presence of protein-containing exosome-like vesicles in all three bee-derived products. Assessing their antibacterial properties, we found that exosome-like vesicles had bacteriostatic, bactericidal and biofilm-inhibiting effects on Staphylococcus aureus. Furthermore, we could demonstrate that mesenchymal stem cells (MSCs) internalize bee-derived exosome-like vesicles and that these vesicles influence their migration potential. In an in vitro wound healing assay, honey and royal jelly exosome-like vesicles increased migration of human MSC, demonstrating their interkingdom activity. Summarizing, we have discovered exosome-like vesicles as a new, active compound in bee pollen, honey and royal jelly.

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Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration

2020 , Juliana González-Sanmiguel , Christina M. A. P. Schuh , Carola Muñoz-Montesino , Pamina Contreras-Kallens , Luis G. Aguayo , Sebastian Aguayo

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Creutzfeldt–Jakob disease (CJD) are brain conditions affecting millions of people worldwide. These diseases are associated with the presence of amyloid-β (Aβ), alpha synuclein (α-Syn) and prion protein (PrP) depositions in the brain, respectively, which lead to synaptic disconnection and subsequent progressive neuronal death. Although considerable progress has been made in elucidating the pathogenesis of these diseases, the specific mechanisms of their origins remain largely unknown. A body of research suggests a potential association between host microbiota, neuroinflammation and dementia, either directly due to bacterial brain invasion because of barrier leakage and production of toxins and inflammation, or indirectly by modulating the immune response. In the present review, we focus on the emerging topics of neuroinflammation and the association between components of the human microbiota and the deposition of Aβ, α-Syn and PrP in the brain. Special focus is given to gut and oral bacteria and biofilms and to the potential mechanisms associating microbiome dysbiosis and toxin production with neurodegeneration. The roles of neuroinflammation, protein misfolding and cellular mediators in membrane damage and increased permeability are also discussed.

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Antibacterial Effect of Honey-Derived Exosomes Containing Antimicrobial Peptides Against Oral Streptococci

2021 , Camila Leiva-Sabadini , Simon Alvarez , Nelson P Barrera , Christina MAP Schuh , Sebastian Aguayo

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