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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Item type:Publication, 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. BarreraSebastian Aguayo7Scopus© Citations 34 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Nanoscale Dynamics of Streptococcal Adhesion to AGE-Modified Collagen(2023) ;C. Leiva-Sabadini ;P. Tiozzo-Lyon ;L. Hidalgo-Galleguillos ;L. RivasA.I. Robles<jats:p> 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. </jats:p>Scopus© Citations 7 1 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 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. SchuhSebastian AguayoScopus© Citations 26 4 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Ultrastructural characterisation of young and aged dental enamel by atomic force microscopy(2022) ;Camila Leiva‐Sabadini ;Christina MAP Schuh ;Nelson P. BarreraSebastian Aguayo37Scopus© Citations 6 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 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-KallensLuis G. Aguayo<jats:p>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.</jats:p>3Scopus© Citations 34 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Potential Novel Strategies for the Treatment of Dental Pulp-Derived Pain: Pharmacological Approaches and Beyond(2019); ;Bruna BensoSebastian Aguayo12 1Scopus© Citations 21 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 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 ZavalaMaroun Khoury<jats:p>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.</jats:p>Scopus© Citations 49 1 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Modulatory Effect of Glycated Collagen on Oral Streptococcal Nanoadhesion(2020); ;B. Benso ;P.A. Naulin ;N.P. BarreraL. Bozec<jats:p> Biofilm-mediated oral diseases such as dental caries and periodontal disease remain highly prevalent in populations worldwide. Biofilm formation initiates with the attachment of primary colonizers onto surfaces, and in the context of caries, the adhesion of oral streptococci to dentinal collagen is crucial for biofilm progression. It is known that dentinal collagen suffers from glucose-associated crosslinking as a function of aging or disease; however, the effect of collagen crosslinking on the early adhesion and subsequent biofilm formation of relevant oral streptococci remains unknown. Therefore, the aim of this work was to determine the impact of collagen glycation on the initial adhesion of primary colonizers such as Streptococcus mutans UA159 and Streptococcus sanguinis SK 36, as well as its effect on the early stages of streptococcal biofilm formation in vitro. Type I collagen matrices were crosslinked with either glucose or methylglyoxal. Atomic force microscopy nanocharacterization revealed morphologic and mechanical changes within the collagen matrix as a function of crosslinking, such as a significantly increased elastic modulus in crosslinked fibrils. Increased nanoadhesion forces were observed for S. mutans on crosslinked collagen surfaces as compared with the control, and retraction curves obtained for both streptococcal strains demonstrated nanoscale unbinding behavior consistent with bacterial adhesin-substrate coupling. Overall, glucose-crosslinked substrates specifically promoted the initial adhesion, biofilm formation, and insoluble extracellular polysaccharide production of S. mutans, while methylglyoxal treatment reduced biofilm formation for both strains. Changes in the adhesion behavior and biofilm formation of oral streptococci as a function of collagen glycation could help explain the biofilm dysbiosis seen in older people and patients with diabetes. Further studies are necessary to determine the influence of collagen crosslinking on the balance between acidogenic and nonacidogenic streptococci to aid in the development of novel preventive and therapeutic treatment against dental caries in these patients. </jats:p>1Scopus© Citations 23 2 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Nanomechanical and Molecular Characterization of Aging in Dentinal Collagen(2022) ;C.M.A.P. Schuh ;C. Leiva-Sabadini ;S. Huang ;N.P. BarreraL. Bozec<jats:p> 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. </jats:p>5Scopus© Citations 7 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Antibacterial Effect of Honey-Derived Exosomes Containing Antimicrobial Peptides Against Oral Streptococci(2021) ;Camila Leiva-Sabadini ;Simon Alvarez ;Nelson P Barrera ;Christina MAP SchuhSebastian AguayoScopus© Citations 39 3