A New Class of Quorum Quenching Molecules from <i>Staphylococcus</i> Species Affects Communication and Growth of Gram-Negative Bacteria

The knowledge that many pathogens rely on cell-to-cell communication mechanisms known as quorum sensing, opens a new disease control strategy: quorum quenching. Here we report on one of the rare examples where Gram-positive bacteria, the ‘Staphylococcus intermedius group’ of zoonotic pathogens, excrete two compounds in millimolar concentrations that suppress the quorum sensing signaling and inhibit the growth of a broad spectrum of Gram-negative beta- and gamma-proteobacteria. These compounds were isolated from Staphylococcus delphini. They represent a new class of quorum quenchers with the chemical formula N-[2-(1H-indol-3-yl)ethyl]-urea and N-(2-phenethyl)-urea, which we named yayurea A and B, respectively. In vitro studies with the N-acyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds caused opposite effects on phosphorylation to those caused by AHL. This explains the quorum quenching activity. Staphylococcal strains producing yayurea A and B clearly benefit from an increased competitiveness in a mixed community.诸多致病菌依赖被称为群体感应（quorum sensing）的细胞间通讯机制这一认知，为疾病防控开辟了全新策略：群体淬灭（quorum quenching）。本研究报道了一例罕见案例：人畜共患病原菌——中间葡萄球菌群（Staphylococcus intermedius group）这类革兰氏阳性（Gram-positive）菌，可分泌两种毫摩尔级浓度的化合物，此类化合物能够抑制群体感应信号通路，并广谱抑制革兰氏阴性β-变形菌与γ-变形菌的生长。上述化合物分离自海豚葡萄球菌（Staphylococcus delphini），它们属于一类全新的群体淬灭剂，化学结构分别为N-[2-(1H-吲哚-3-基)乙基]-脲与N-(2-苯乙基)-脲，我们将其分别命名为yayurea A与yayurea B。通过对哈氏弧菌（V. harveyi）的N-酰基高丝氨酸内酯（AHL）响应受体LuxN开展的体外实验表明，这两种化合物对磷酸化的作用与AHL完全相反，这一现象解释了其群体淬灭活性的作用机制。能够产生yayurea A与B的葡萄球菌菌株，在混合菌群环境中可通过提升自身竞争力而获得显著生存优势。