Centro de Biotecnologia do Estado do Rio Grande do Sul, Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, 91501-970, Brazil.
Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre-RS, 90610-000, Brazil.
Sci Rep. 2017 Jun 6;7(1):2823. doi: 10.1038/s41598-017-02712-1.
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.
金黄色葡萄球菌是一种机会致病菌，与多种危及生命的感染有关，但抗菌药物耐药性限制了其治疗选择。我们在此报告，杨梅素，而非其糖基化形式，可显著降低几种金黄色葡萄球菌毒力因子的产生，包括黏附、生物膜形成、溶血和金黄色素产生，而不影响生长。杨梅素影响表面蛋白和分泌蛋白，表明其作用与抑制agr 群体感应系统无关。对与毒力相关的基因表达的分析和参与发病机制的关键蛋白的计算模拟表明，杨梅素下调了 saeR 全局调节因子，并与葡萄球菌表面蛋白 A 和α-溶血素相互作用。此外，Myr 在大蜡螟模型中对金黄色葡萄球菌感染提供了显著的保护作用。本研究结果揭示了 Myr 作为一种替代的多靶点抗毒力候选药物，用于控制金黄色葡萄球菌致病性的潜力。
