PDF(Pubmed)
Abstract：
Many bacterial surface proteins and carbohydrates are modified with phosphorylcholine (ChoP), which contributes to host mimicry and can also promote colonization and survival in the host. However, the ChoP biosynthetic pathways that are used in bacterial species that express ChoP have not been systematically studied. For example, the well-studied Lic-1 pathway is absent in some ChoP-expressing bacteria, such as Neisseria meningitidis and Neisseria gonorrhoeae. This raises a question as to the origin of the ChoP used for macromolecule biosynthesis in these species. In the current study, we used in silico analyses to identify the potential pathways involved in ChoP biosynthesis in genomes of the 26 bacterial species reported to express a ChoP-modified biomolecule. We used the four known ChoP biosynthetic pathways and a ChoP transferase as search terms to probe for their presence in these genomes. We found that the Lic-1 pathway is primarily associated with organisms producing ChoP-modified carbohydrates, such as lipooligosaccharide. Pilin phosphorylcholine transferase A (PptA) homologs were detected in all bacteria that express ChoP-modified proteins. Additionally, ChoP biosynthesis pathways, such as phospholipid N-methyltransferase (PmtA), phosphatidylcholine synthase (Pcs), or the acylation-dependent phosphatidylcholine biosynthesis pathway, which generate phosphatidylcholine, were also identified in species that produce ChoP-modified proteins. Thus, a major finding of this study is the association of a particular ChoP biosynthetic pathway with a cognate, target ChoP-modified surface factor; i.e., protein versus carbohydrate. This survey failed to identify a known biosynthetic pathway for some species that express ChoP, indicating that a novel ChoP biosynthetic pathway(s) may remain to be identified. IMPORTANCE The modification of bacterial surface virulence factors with phosphorylcholine (ChoP) plays an important role in bacterial virulence and pathogenesis. However, the ChoP biosynthetic pathways in bacteria have not been fully understood. In this study, we used in silico analysis to identify potential ChoP biosynthetic pathways in bacteria that express ChoP-modified biomolecules and found the association between a specific ChoP biosynthesis pathway and the cognate target ChoP-modified surface factor.
摘要：
许多细菌表面蛋白和碳水化合物被磷酸胆碱（ChoP）修饰，这有助于宿主模仿，也可以促进宿主的定植和生存。然而,在表达ChoP的细菌物种中使用的ChoP生物合成途径尚未被系统研究。例如,在一些表达ChoP的细菌中缺乏经过充分研究的Lic-1途径，如脑膜炎奈瑟菌和淋病奈瑟菌。这提出了一个问题，即在这些物种中用于大分子生物合成的ChoP的起源。在目前的研究中,我们使用计算机模拟分析来确定26种据报道表达ChoP修饰的生物分子的细菌的基因组中ChoP生物合成的潜在途径。我们使用四种已知的ChoP生物合成途径和ChoP转移酶作为搜索项来探测它们在这些基因组中的存在。我们发现Lic-1通路主要与产生ChoP修饰的碳水化合物的生物体有关，如脂寡糖。在所有表达ChoP修饰蛋白的细菌中都检测到了Pilin磷酰胆碱转移酶A（PptA）同源物。此外,ChoP生物合成途径，如磷脂N-甲基转移酶（PMTA），磷脂酰胆碱合酶（Pcs），或酰化依赖性磷脂酰胆碱生物合成途径，产生磷脂酰胆碱，在产生ChoP修饰蛋白的物种中也被鉴定。因此，这项研究的一个主要发现是特定的ChoP生物合成途径与同源物的关联，目标ChoP修饰的表面因子；即，蛋白质与碳水化合物。这项调查未能确定一些表达ChoP的物种的已知生物合成途径，这表明新的ChoP生物合成途径可能仍有待鉴定。重要性用磷酸胆碱（ChoP）修饰细菌表面毒力因子在细菌毒力和发病机理中起重要作用。然而,细菌中的ChoP生物合成途径尚未完全了解。在这项研究中,我们在计算机模拟分析中鉴定了表达ChoP修饰的生物分子的细菌中潜在的ChoP生物合成途径,并发现了特定的ChoP生物合成途径与同源靶ChoP修饰的表面因子之间的关联.
