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The Rgg1518 transcriptional regulator is a necessary facet of sugar metabolism and virulence in Streptococcus pneumoniae
Molecular Microbiology ( IF 3.6 ) Pub Date : 2021-07-30 , DOI: 10.1111/mmi.14788
Bushra Shlla 1, 2 , Ozcan Gazioglu 1 , Sulman Shafeeq 3 , Irfan Manzoor 3 , Oscar P Kuipers 3 , Andrew Ulijasz 4 , N Luisa Hiller 5 , Peter W Andrew 1 , Hasan Yesilkaya 1
Affiliation  

Rggs are a group of transcriptional regulators with diverse roles in metabolism and virulence. Here, we present work on the Rgg1518/SHP1518 quorum sensing system of Streptococcus pneumoniae. The activity of Rgg1518 is induced by its cognate peptide, SHP1518. In vitro analysis showed that the Rgg1518 system is active in conditions rich in galactose and mannose, key nutrients during nasopharyngeal colonization. Rgg1518 expression is highly induced in the presence of these sugars and its isogenic mutant is attenuated in growth on galactose and mannose. When compared with other Rgg systems, Rgg1518 has the largest regulon on galactose. On galactose it controls up- or downregulation of a functionally diverse set of genes involved in galactose metabolism, capsule biosynthesis, iron metabolism, protein translation, as well as other metabolic functions, acting mainly as a repressor of gene expression. Rgg1518 is a repressor of capsule biosynthesis, and binds directly to the capsule regulatory region. Comparison with other Rggs revealed inter-regulatory interactions among Rggs. Finally, the rgg1518 mutant is attenuated in colonization and virulence in a mouse model of colonization and pneumonia. We conclude that Rgg1518 is a virulence determinant that contributes to a regulatory network composed of multiple Rgg systems.

中文翻译:

Rgg1518 转录调节因子是肺炎链球菌糖代谢和毒力的必要方面

Rggs 是一组转录调节因子,在代谢和毒力中具有不同的作用。在这里,我们介绍了关于肺炎链球菌的 Rgg1518/SHP1518 群体感应系统的工作. Rgg1518 的活性是由其同源肽 SHP1518 诱导的。体外分析表明,Rgg1518 系统在富含半乳糖和甘露糖(鼻咽定植过程中的关键营养素)的条件下具有活性。Rgg1518 表达在这些糖的存在下被高度诱导,其同基因突变体在半乳糖和甘露糖上的生长减弱。与其他 Rgg 系统相比,Rgg1518 具有最大的半乳糖调节子。在半乳糖上,它控制一组功能多样的基因的上调或下调,这些基因涉及半乳糖代谢、胶囊生物合成、铁代谢、蛋白质翻译以及其他代谢功能,主要作为基因表达的阻遏物。Rgg1518 是胶囊生物合成的阻遏物,直接与胶囊调节区结合。与其他 Rggs 的比较揭示了 Rggs 之间的监管相互作用。最后,rgg1518突变体在定植和肺炎小鼠模型中的定植和毒力减弱。我们得出结论,Rgg1518 是一种毒力决定因素,有助于形成由多个 Rgg 系统组成的监管网络。
更新日期:2021-09-23
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