2-(2-Methyl-2-nitrovinyl)furan but Not Furvina Interfere with Staphylococcus aureus Agr Quorum-Sensing System and Potentiate the Action of Fusidic Acid against Biofilms

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Diana Oliveira (Author) Other; Anabela Borges (Author) FEUP; Reinaldo Molina Ruiz (Author) Other; Zenaida Rodríguez Negrín (Author) Other; Simona Distinto (Author) Other; Fernanda Borges (Author) FCUP; Manuel Simões (Author) FEUP

Journal

Title: International Journal Of Molecular Sciences

Vol. 22 No. 9

Pages: 1-15

ISSN: 1661-6596

Publisher: MDPI

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Associated Projects

LEPABE - Financiamento Plurianual 2020-2023 da Unidade de I&D LEPABE - Laboratório de Engenharia de Processos, Ambiente, Biotecnologia e Energia

Biocide_for_Biofilm - Desenvolvimento de novas soluções biocidas para o controlo efetivo de biofilmes

Other information

Authenticus ID: P-00T-9V4

DOI: 10.3390/ijms22020613

Abstract (EN): Quorum sensing (QS) plays an essential role in the production of virulence factors, in biofilm formation and antimicrobial resistance. Consequently, inhibiting QS is being considered a promising target for antipathogenic/anti-virulence therapies. This study aims to screen 2-nitrovinylfuran derivatives structurally related to Furvina (a broad-spectrum antibiotic already used for therapeutic purposes) for their effects on QS and in biofilm prevention/control. Furvina and four 2-nitrovinylfuran derivatives (compounds 1-4) were tested to assess the ability to interfere with QS of Staphylococcus aureus using bioreporter strains (S. aureus ALC1742 and ALC1743). The activity of Furvina and the most promising quorum-sensing inhibitor (QSI) was evaluated in biofilm prevention and in biofilm control (combined with fusidic acid). The biofilms were further characterized in terms of biofilm mass, viability and membrane integrity. Compound 2 caused the most significant QS inhibition with reductions between 60% and 80%. Molecular docking simulations indicate that this compound interacts preferentially with the protein hydrophobic cleft in the LytTR domain of AgrA pocket. Metabolic inactivations of 40% for S. aureus ALC1742 and 20% for S. aureus ALC1743 were reached. A 24 h-old biofilm formed in the presence of the QSI increased the metabolic inactivation by fusidic acid to 80%, for both strains. The overall results highlight the effects of compound 2 as well as the potential of combining QSI with in-use antibiotics for the management of skin and soft tissues infections.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15