Post-translational modification by the Pgf glycosylation machinery modulates Streptococcus mutans OMZ175 physiology and virulence.
Post-translational modification by the Pgf glycosylation machinery modulates Streptococcus mutans OMZ175 physiology and virulence.
复制标题
Pgf 糖基化机制的翻译后修饰可调节变形链球菌 OMZ175 的生理学和毒力。
DOI：
10.1111/mmi.15190
复制
发表时间：
2023
影响因子：
3.6
通讯作者：
Lem
中科院分区：
文献类型：
--
作者：
deMojanadiCologna,Nicholas;Andresen,Silke;Samaddar,Sandip;Archer-Hartmann,Stephanie;Rogers,AshleyMarie;Kajfasz,JessicaK;Ganguly,Tridib;Garcia,BrunaA;Saengpet,Irene;Peterson,AlexandraM;Azadi,Parastoo;Szymanski,ChristineM;Lem
变形链球菌通常与龋齿有关，形成生物膜的能力对其致病性至关重要。我们最近发现了s的Pgf糖基化机制。突变体，负责翻译后表面相关粘附素Cnm和WapA的修饰。由于四基因操纵子（pgfS‐pggf1‐pgfE‐pgfM2）是这些基因的一部分。我们假设Pgf系统的范围超出了Cnm和WapA糖基化。硅分析和tunicamycin敏感性试验表明Pgf机制和鼠李糖-葡萄糖多糖合成途径之间存在功能重叠。Pgf突变体的表型特征（ΔpgfS， ΔpgfE， ΔpgfM1， ΔpgfM2和Δpgf）表明，Pgf系统对人类唾液中生物膜的形成、表面电荷、膜稳定性和存活都很重要。此外，在大鼠口腔定植模型中，整个操纵子的缺失（Δpgfstrain）导致定植明显受损。以Cnm为模型，我们发现Cnm被N -乙酰基己糖胺大量修饰，但随着PgfS糖基转移酶的失活，Cnm被大量磷酸化，这表明这两种翻译后修饰机制之间存在串扰。我们的研究结果表明，Pgf机制对s的多个方面都有贡献。可能超越Cnm和WapA糖基化的突变病理学。
Streptococcus mutansis commonly associated with dental caries and the ability to form biofilms is essential for its pathogenicity. We recently identified the Pgf glycosylation machinery ofS. mutans, responsible for the post‐translational modification of the surface‐associated adhesins Cnm and WapA. Since the four‐genepgfoperon (pgfS‐pgfM1‐pgfE‐pgfM2) is part of theS. mutanscore genome, we hypothesized that the scope of the Pgf system goes beyond Cnm and WapA glycosylation. In silico analyses and tunicamycin sensitivity assays suggested a functional overlap between the Pgf machinery and the rhamnose‐glucose polysaccharide synthesis pathway. Phenotypic characterization ofpgfmutants (ΔpgfS, ΔpgfE, ΔpgfM1, ΔpgfM2, and Δpgf) revealed that the Pgf system is important for biofilm formation, surface charge, membrane stability, and survival in human saliva. Moreover, deletion of the entirepgfoperon (Δpgfstrain) resulted in significantly impaired colonization in a rat oral colonization model. Using Cnm as a model, we showed that Cnm is heavily modified with N‐acetyl hexosamines but it becomes heavily phosphorylated with the inactivation of the PgfS glycosyltransferase, suggesting a crosstalk between these two post‐translational modification mechanisms. Our results revealed that the Pgf machinery contributes to multiple aspects ofS. mutanspathobiology that may go beyond Cnm and WapA glycosylation.