Abstract

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.

Highlights

  • Staphylococcus aureus is an important human opportunistic pathogen involved in a wide range of human infections

  • We examined the effect of Myr and of its glycosylated form, myricitrin (Myr-gly- Fig. 1h), on several virulence factors produced by S. aureus and the potencial of the flavonol to protect the host during infection using the in vivo Galleria mellonella model

  • Scanning electron microscopy (SEM) images showed decreased biofilm formation on a hydrophobic polystyrene surface when S. aureus cells were exposed to Myr in comparison to untreated cells

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Summary

Introduction

Staphylococcus aureus is an important human opportunistic pathogen involved in a wide range of human infections. Through binding to the host membrane, the monomer oligomerizes to form a 232.4 kDa membrane-inserted heptamer This pore-forming toxin has been reported as an important protein that mediates tissue damage promoted by S. aureus. Myricetin (Myr), 3,5,7,3′,4′,5′-hexahydroxyflavone (Fig. 1a), is a flavonoid commonly ingested through human diets such as fruits, vegetables, tea, berries and red wine This flavonol has been proven to possess various beneficial pharmacological properties, including anti-oxidative and cytoprotective effects, anti-carcinogenic actions, antiviral properties as well as antiplatelet, anti-inflammation and anti-hyperlipidemia activities[18, 19]. We examined the effect of Myr and of its glycosylated form, myricitrin (Myr-gly- Fig. 1h), on several virulence factors produced by S. aureus and the potencial of the flavonol to protect the host during infection using the in vivo Galleria mellonella model

Methods
Results
Conclusion

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