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Myricetin protects Galleria mellonella against Staphylococcus aureus infection and inhibits multiple virulence factors

Laura Nunes SilvaCentro de Biotecnologia do Estado do Rio Grande do Sul, Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, 91501-970, BrazilGabriel C. A. da HoraDepartmento de Química Fundamental, Universidade Federal de Pernambuco, Recife-PE, 50670-901, BrazilThereza A. SoaresDepartment of Chemistry, Umeå University, 90187, Umeå, SwedenMartin S. BojerDepartment of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, 1870, DenmarkHanne IngmerDepartment of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, 1870, DenmarkAlexandre José MacêdoCentro de Biotecnologia do Estado do Rio Grande do Sul, Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, 91501-970, Brazil. [email protected]Danielle da Silva TrentinCentro de Biotecnologia do Estado do Rio Grande do Sul, Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, 91501-970, Brazil

2017en

ABI

Annotatsiya

Staphylococcus aureus is an opportunistic pathogen related to a variety of life-threatening infections but for which antimicrobial resistance is liming the treatment options. We report here that myricetin, but not its glycosylated form, can remarkably decrease the production of several S. aureus virulence factors, including adhesion, biofilm formation, hemolysis and staphyloxanthin production, without interfering with growth. Myricetin affects both surface proteins and secreted proteins which indicate that its action is unrelated to inhibition of the agr quorum sensing system. Analysis of virulence related gene expression and computational simulations of pivotal proteins involved in pathogenesis demonstrate that myricetin downregulates the saeR global regulator and interacts with sortase A and α-hemolysin. Furthermore, Myr confers a significant degree of protection against staphylococcal infection in the Galleria mellonella model. The present findings reveal the potential of Myr as an alternative multi-target antivirulence candidate to control S. aureus pathogenicity.

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DOI: 10.1038/s41598-017-02712-1

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