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Optimizing blue light-activated disinfection for Endodontic therapy

English title Optimizing blue light-activated disinfection for Endodontic therapy
Applicant Bouillaguet Serge
Number 149962
Funding scheme Project funding (Div. I-III)
Research institution Section de Médecine Dentaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Dentistry
Start/End 01.02.2014 - 31.01.2018
Approved amount 298'244.00
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Keywords (3)

Blue light-activated disinfection; Endodontic infection; Metagenomics

Lay Summary (French)

Lead
La photothérapie antibactérienne permet d'inactiver les agents pathogènes impliqués dans la carie dentaire et les maladies d’origine endodontique et parodontale. L'efficacité de certains photo-sensibilisateurs activés par la lumière bleue reste à améliorer et notamment sur les biofilms formés de bactéries Gram-négatives
Lay summary

En Médecinedentaire, la photothérapie antibactérienne a été proposée comme moyen thérapeutiquecomplémentaire ou alternatif pour inactiver les agents pathogènes impliquésdans la carie dentaire et les maladies d’origine endodontique et parodontale. Laphotothérapie antibactérienne est basée sur l’interaction d’un agentphotosensible (photo-sensibilisateur) avec une source lumineuse de longueur d’ondeappropriée qui produit des dérivés oxygénés bactéricides. Nos travaux ont misen évidence l’effet létal de plusieurs photo-sensibilisateurs activés par lalumière bleue sur des bactéries Gram-positives présentes dans la carie dentaireet des infections endodontiques réfractaires. En outre, il a été démontré qu’àdoses bactéricides, ces agents photo-activables n’entraînent pas d’effetscytotoxiques envers les cellules hôte, démontrant ainsi un index thérapeutiquefavorable. Malgré ces résultats encourageants, un manque d’efficacité enversles biofilms bactériens a été démontré en comparaison avec les effets observéssur les mêmes agents pathogènes en mode de croissance planctonique. Une absenced’effet bactéricide a également été rapportée pour certaines souchesendodontiques Gram-négatives.

Dansce projet, nous nous proposons de développer des formulations dephoto-sensibilisateurs plus efficaces envers les principales bactéries oralesGram-négatives. Nous souhaitons également améliorer nos connaissances desbiofilms oraux multi-espèces et développer des modèles permettant de mieuxcontrôler l’efficacité de la photothérapie antibactérienne; une analyse métagénomique de l’écosystème endodontique permettrait de définir de façon plusprécise le contenu du système canalaire infecté et de raffiner l’utilisation dela photothérapie antibactérienne.

Direct link to Lay Summary Last update: 15.01.2014

Lay Summary (English)

Lead
Optimizing blue light-activated disinfection for Endodontic therapy
Lay summary

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Direct link to Lay Summary Last update: 15.01.2014

Responsible applicant and co-applicants

Employees

Publications

Publication
Enzyme-mediated photoinactivation of Enterococcus faecalis using Rose Bengal-acetate.
(2018), Enzyme-mediated photoinactivation of Enterococcus faecalis using Rose Bengal-acetate., in J Photochem Photobiol B, 84-90.
Rose bengal uptake by E. faecalis and F. nucleatum and light-mediated antibacterial activity measured by flow cytometry.
Manoil Daniel, Filieri Anna, Schrenzel Jacques, Bouillaguet Serge, Manoil Daniel, Filieri Anna, Schrenzel Jacques, Bouillaguet Serge (2016), Rose bengal uptake by E. faecalis and F. nucleatum and light-mediated antibacterial activity measured by flow cytometry., in Journal of photochemistry and photobiology. B, Biology, 162, 258-65.
Repeated exposures to blue light-activated eosin Y enhance inactivation of E. faecalis biofilms, in vitro.
Marinic Karlo, Manoil Daniel, Filieri Anna, Wataha John C, Schrenzel Jacques, Lange Norbert, Bouillaguet Serge, Marinic Karlo, Manoil Daniel, Filieri Anna, Wataha John C, Schrenzel Jacques, Lange Norbert, Bouillaguet Serge (2015), Repeated exposures to blue light-activated eosin Y enhance inactivation of E. faecalis biofilms, in vitro., in Photodiagnosis and photodynamic therapy, 12(3), 393-400.
Antimicrobial activity and cytotoxicity of 3 photosensitizers activated with blue light.
Bulit Florence, Grad Iwona, Manoil Daniel, Simon Stéphane, Wataha John C, Filieri Anna, Feki Anis, Schrenzel Jacques, Lange Norbert, Bouillaguet Serge, Bulit Florence, Grad Iwona, Manoil Daniel, Simon Stéphane, Wataha John C, Filieri Anna, Feki Anis, Schrenzel Jacques, Lange Norbert, Bouillaguet Serge (2014), Antimicrobial activity and cytotoxicity of 3 photosensitizers activated with blue light., in Journal of endodontics, 40(3), 427-31.
Flow cytometric assessment of Streptococcus mutans viability after exposure to blue light-activated curcumin.
Manoil Daniel, Filieri Anna, Gameiro Cécile, Lange Norbert, Schrenzel Jacques, Wataha John C, Bouillaguet Serge, Manoil Daniel, Filieri Anna, Gameiro Cécile, Lange Norbert, Schrenzel Jacques, Wataha John C, Bouillaguet Serge (2014), Flow cytometric assessment of Streptococcus mutans viability after exposure to blue light-activated curcumin., in Photodiagnosis and photodynamic therapy, 11(3), 372-9.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
International Association for Dental Research- Pan European Region Poster Repeated Exposures to Photo-activated Eosin Y Affect Enterococcus faecalis Viability 10.09.2014 Dubrovnik, Croatia Bouillaguet Serge;
International Association for Dental Research- Pan European Region Poster Antibacterial Activity of Light-activated Eosin Y against Enterococcus faecalis Biofilms 10.09.2014 Dubrovnik, Croatia Bouillaguet Serge;
International Association for Dental Research- Pan European Region Poster Survival of Streptococcus mutans exposed to blue light-activated curcumin 10.09.2014 Dubrovnik, Croatia Bouillaguet Serge;
Microbiology retreat of the Centre of Excellence in Bacteriology of the University of Geneva (CEBUG) Poster Assessment of E. faecalis and F. nucleatum oxidative stress and viability by flow cytometry 21.05.2014 Villars sur Ollon, Switzerland Bouillaguet Serge;
Summer School of the Swiss Society for Endodontology Talk given at a conference Flow cytometric assessment of bacterial viability 07.05.2014 Solothurn, Switzerland Bouillaguet Serge;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
9ème journées de Microbiologie de la Faculté de Médecine de Genève Talk 15.09.2016 Genève, Switzerland Bouillaguet Serge;


Communication with the public

Communication Title Media Place Year
Talks/events/exhibitions Flore Buccale: Equilibre délicat entre Ying et Yang Western Switzerland 2016

Associated projects

Number Title Start Funding scheme
119938 Blue light-mediated inactivation of endodontic pathogens 01.09.2008 Project funding (Div. I-III)
119938 Blue light-mediated inactivation of endodontic pathogens 01.09.2008 Project funding (Div. I-III)

Abstract

In our previous research project (# 310000 11993) we generated the following data that suggest that blue light -mediated PAD is an appealing option for endodontic disinfection. First, we have identified several photosensitizers which generate ROS upon blue light irradiation and have established the in vitro efficacy of these photosensitizers as antimicrobial agents against major Gram-positive endodontic pathogens. Second, we have verified that these photo-activated chemicals do not elicit unwanted toxicity towards resident cells at bactericidal concentrations, thus indicating a favorable therapeutic index. Although these key experiments have demonstrated that blue light-activated disinfection has the potential to induce lethal oxidative stresses in bacteria with minimum adverse effects to host cells, several limitations have also been identified. Among these were a poor efficiency against some Gram-negative pathogens and a reduced efficiency on bacterial biofilms compared to planktonic suspensions. Further, most recent research using culture-independent methods has severely questioned the relevance of the endodontic microbiota previously identified by culture-based methods. Therefore, in the current proposal, we will:•Develop photosensitizer-conjugates required for enhanced ROS production and improved efficacy against gram negative endodontic pathogens •Improve our understanding of antimicrobial efficacy using 3D biofilm models and validate our in vitro results using metagenomic approaches on clinical samples We are hopeful that the combination of the unique electromagnetic properties of blue light with optimized photosensitizers will synergize to make blue light-mediated PAD a successful treatment for endodontic infection. Furthermore, the unique structure of this project that combines, dentistry, chemistry and microbiology will provide us with new knowledge on endodontic infections and antibacterial treatments.
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