Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 10691 Stockholm, Sweden.
Sci Rep. 2017 Mar 17;7:44902. doi: 10.1038/srep44902.
Streptococcus pyogenes an adapted human pathogen asymptomatically colonizes the nasopharynx, among other polymicrobial communities. However, information on the events leading to the colonization and expression of virulence markers subject to interspecies and host-bacteria interactions are limited. The interference of acyl homoserine lactones (AHLs) with the hemolytic activity and viability of S. pyogenes M6 S165 was examined. AHLs, with fatty acid side chains ≥12 carbon atoms, inhibited hemolytic activity by downregulating the expression of the sag operon involved in the production of streptolysin S. Inhibitory AHLs upregulated the expression of transcriptional regulator LuxR. Electrophoretic mobility shift assays revealed the interaction of LuxR with the region upstream of sagA. AHL-mediated bactericidal activity observed at higher concentrations (mM range) was an energy-dependent process, constrained by the requirement of glucose and iron. Ferrichrome transporter FtsABCD facilitated transport of AHLs across the streptococcal membrane. The study demonstrates a previously unreported role for AHLs in S. pyogenes virulence.
化脓链球菌(Streptococcus pyogenes)作为一种适应人体的病原体,能够在鼻咽等多种微生物群落中无症状定植。然而,关于导致定植和表达毒力标志物的事件的信息,受到种间和宿主-细菌相互作用的限制。本研究检测了酰基高丝氨酸内酯(AHLs)对化脓链球菌 M6 S165 的溶血活性和活力的干扰作用。具有≥12 个碳原子的脂肪酸侧链的 AHL 通过下调参与溶血素 S 产生的 sag 操纵子的表达,抑制了溶血活性。抑制性 AHL 上调了转录调节因子 LuxR 的表达。电泳迁移率变动分析显示了 LuxR 与 sagA 上游区域的相互作用。在更高浓度(mM 范围)下观察到的 AHL 介导的杀菌活性是一种能量依赖性过程,受到葡萄糖和铁的需求的限制。铁载体 FtsABCD 促进了 AHL 穿过链球菌膜的运输。本研究证明了 AHLs 在化脓链球菌毒力中的一个以前未被报道的作用。