ABSTRACT

Global transcriptional regulators are prevalent in gram-positive pathogens. The transcriptional regulators of the Mga/AtxA family regulate target gene expression by directly binding to the promoter regions, that results in the coordinated expression of virulence factors. The spd_1587 gene of Streptococcus pneumoniae strain D39 encodes MgaSpn, which shares sequence similarity with global transcriptional regulators of the Mga/AtxA family. In this study, we demonstrated that MgaSpn regulates the biosynthesis of the capsule and phosphorylcholine, which play key roles in disease severity in S. pneumoniae infections. MgaSpn directly binds to the cps and lic1 promoters and affects the biosynthesis of the capsule and phosphorylcholine. MgaSpn binds to two specific sites on the promoter of cps, one of which contains the −35 box of the promoter, with high affinity. Consistently, low-molecular-weight capsule components were observed in the mgaSpn-null mutant strain. Moreover, we found that phosphorylcholine content was notably increased in the unencapsulated mgaSpn mutant strain. The mgaSpn null mutant caused more severe systemic disease than the parental strain D39. These findings indicate that the pneumococcal MgaSpn protein can inhibit capsule and phosphorylcholine production, thereby affecting the virulence of S. pneumoniae.

摘要

全球转录调节因子普遍存在于革兰氏阳性病原体中。Mga/AtxA 家族的转录调节因子通过直接与启动子区域结合来调节靶基因的表达，从而导致毒力因子的协调表达。肺炎链球菌菌株 D39的spd_1587基因编码 Mga Spn，它与 Mga/AtxA 家族的全球转录调节因子具有序列相似性。在这项研究中，我们证明了 Mga Spn调节胶囊和磷酸胆碱的生物合成，它们在肺炎链球菌感染的疾病严重程度中起关键作用。Mga Spn直接绑定到cps和lic1促进并影响胶囊和磷酸胆碱的生物合成。Mga Spn与cps启动子上的两个特定位点结合，其中一个包含启动子的-35 框，具有高亲和力。一致地，在mgaSpn- null 突变株中观察到低分子量胶囊成分。此外，我们发现磷酸胆碱含量在未封装的mgaSpn突变株中显着增加。mgaSpn无效突变体比亲本菌株 D39 引起更严重的全身性疾病。这些发现表明，肺炎球菌 Mga Spn蛋白可以抑制荚膜和磷酸胆碱的产生，从而影响肺炎球菌的毒力。肺炎链球菌。