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

TY - JOUR

T1 - Myricetin protects Galleria mellonella against Staphylococcus aureus infection and inhibits multiple virulence factors

AU - Nogueira-Silva, L

AU - Da Hora, G. C.A.

AU - Soares, Goncalo Teofilo Afonso Pinheiro

AU - Bojer, M. S.

AU - Ingmer, H.

AU - Macedo, A. J.

AU - Trentin, D. S.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-017-02712-1

DO - 10.1038/s41598-017-02712-1

M3 - Journal article

C2 - 28588273

AN - SCOPUS:85020476518

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 2823

ER -