Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, The University of Georgia, Athens, Georgia, USA.
Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, The University of Georgia, Athens, Georgia, USA
J Bacteriol. 2021 Mar 8;203(7). doi: 10.1128/JB.00389-20.
The pneumococcal serine-rich repeat protein (PsrP) is a high-molecular-weight, glycosylated adhesin that promotes the attachment of to host cells. PsrP, its associated glycosyltransferases (GTs), and dedicated secretion machinery are encoded in a 37-kb genomic island that is present in many invasive clinical isolates of PsrP has been implicated in establishment of lung infection in murine models, although specific roles of the PsrP glycans in disease progression or bacterial physiology have not been elucidated. Moreover, enzymatic specificities of associated glycosyltransferases are yet to be fully characterized. We hypothesized that the glycosyltransferases that modify PsrP are critical for the adhesion properties and infectivity of Here, we characterize the putative locus glycosyltransferases responsible for PsrP glycosylation. We also begin to elucidate their roles in virulence. We show that four glycosyltransferases within the locus are indispensable for biofilm formation, lung epithelial cell adherence, and establishment of lung infection in a mouse model of pneumococcal pneumonia. PsrP has previously been identified as a necessary virulence factor for many serotypes of and studied as a surface glycoprotein. Thus, studying the effects on virulence of each glycosyltransferase (GT) that builds the PsrP glycan is of high importance. Our work elucidates the influence of GTs We have identified at least four GTs that are required for lung infection, an indication that it is worthwhile to consider glycosylated PsrP as a candidate for serotype-independent pneumococcal vaccine design.
肺炎链球菌丝氨酸丰富重复蛋白（PsrP）是一种高分子量、糖基化的黏附素，可促进 黏附于宿主细胞。PsrP、其相关糖基转移酶（GT）和专用分泌机制都编码在一个 37kb 的基因组岛中，该基因组岛存在于许多侵袭性临床分离株中。PsrP 已被牵连到肺部感染的建立中，尽管 PsrP 聚糖在疾病进展或细菌生理方面的具体作用尚未阐明。此外，相关糖基转移酶的酶特异性尚未完全表征。我们假设修饰 PsrP 的糖基转移酶对于 的黏附特性和感染性至关重要。在这里，我们对负责 PsrP 糖基化的假定 基因座糖基转移酶进行了表征。我们还开始阐明它们在 毒力中的作用。我们表明， 基因座内的四个糖基转移酶对于生物膜形成、肺上皮细胞黏附和在肺炎链球菌肺炎小鼠模型中肺部感染的建立都是必不可少的。PsrP 先前已被鉴定为许多 血清型的必要毒力因子，并被作为表面糖蛋白进行研究。因此，研究构建 PsrP 聚糖的每个糖基转移酶（GT）对毒力的影响非常重要。我们的工作阐明了 GTs 的影响。我们已经确定了至少四个 GT 是肺部感染所必需的，这表明有必要将糖基化的 PsrP 作为血清型独立肺炎球菌疫苗设计的候选物进行考虑。
