Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids

Autor: Miglė Žiemytė, Sergio Martínez Cuesta, Jaione Valle, Beatriz Rapún-Araiz, Iñigo Lasa, Alex Mira, Carmen Gil, Leticia Matilla-Cuenca
Přispěvatelé: Universidad Pública de Navarra. Departamento de Ciencias de la Salud, Nafarroako Unibertsitate Publikoa. Osasun Zientziak Saila, Gobierno de Navarra / Nafarroako Gobernua, PI011 KILL-BACT, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Diputación Foral de Navarra
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Academica-e: Repositorio Institucional de la Universidad Pública de Navarra
Universidad Pública de Navarra
Scientific Reports
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Academica-e. Repositorio Institucional de la Universidad Pública de Navarra
Popis: The opportunistic pathogen Staphylococcus aureus is responsible for causing infections related to indwelling medical devices, where this pathogen is able to attach and form biofilms. The intrinsic properties given by the self-produced extracellular biofilm matrix confer high resistance to antibiotics, triggering infections difficult to treat. Therefore, novel antibiofilm strategies targeting matrix components are urgently needed. The Biofilm Associated Protein, Bap, expressed by staphylococcal species adopts functional amyloid-like structures as scaffolds of the biofilm matrix. In this work we have focused on identifying agents targeting Bap-related amyloid-like aggregates as a strategy to combat S. aureus biofilm-related infections. We identified that the flavonoids, quercetin, myricetin and scutellarein specifically inhibited Bap-mediated biofilm formation of S. aureus and other staphylococcal species. By using in vitro aggregation assays and the cell-based methodology for generation of amyloid aggregates based on the Curli-Dependent Amyloid Generator system (C-DAG), we demonstrated that these polyphenols prevented the assembly of Bap-related amyloid-like structures. Finally, using an in vivo catheter infection model, we showed that quercetin and myricetin significantly reduced catheter colonization by S. aureus. These results support the use of polyphenols as anti-amyloids molecules that can be used to treat biofilm-related infections.
This research was supported by Grants RTI2018-096011-B-I00 from Ministry of Science and Innovation and PI011 KILL-BACT from the Government of Navarra.
Databáze: OpenAIRE