The role of protein acetylation in Streptococcus gordonii biofilms

项目摘要/摘要 牙菌斑是人类口腔中的一个多菌群落，可导致多发性 口腔疾病。与许多其他多物种微生物群落一样，这些微生物 在不同的人中，组成的牙菌斑在空间上的组织方式相似，这表明 管理这些社区发展的力量是保守的。链球菌 Gordonii被认为在牙菌斑的形成中起着关键作用，因为它 快速结合唾液覆盖的口腔表面的能力，有助于晚期牙菌斑的定植 加入日益成熟的社区。生物膜中戈登葡萄球菌细胞的rna-seq分析 大约10%的基因与浮游生物相比有差异表达 对口单位。特别有趣的是，生物膜来源的细胞上调了SGO_2031，它编码 N-赖氨酸乙酰基转移酶，GCN5相关N-乙酰基转移酶成员 (蚊虫)一家。SGO_2031缺失导致单种生物膜形成缺陷 与野生型亲本菌株相比，由于多聚γ-γ的表达减少 谷氨酸基因(PgsA)，它与胞外物质的产生有关 多糖类。我们的初步数据表明，感受器组氨酸激酶的乙酰化 SGO_0299基因调控pgsA转录和生物膜形成。这项提议将 SGO_0299乙酰化对其同源物磷酸化能力的影响 反应调节因子SGO_0298最终影响EPS的产生和生物膜的形成。 戈登葡萄球菌作为牙齿早期定植生物在口腔生物膜发育中的重要作用 ，我们将建立一个小鼠模型系统来研究SGO_2031是如何依赖的 乙酰化影响戈登葡萄球菌定植和塑造口腔微生物群落的能力。

Project Summary/Abstract Dental plaque is a polymicrobial community of the human mouth that can contribute to multiple oral diseases. As with many other multispecies microbial communities, the microorganisms that make up dental plaque are spatially organized similarly among different people, suggesting that the forces that govern the development of these communities are conserved. Streptococcus gordonii has been hypothesized to play a crucial role in dental plaque development due to its ability to rapidly bind the saliva-coated oral surfaces aiding late colonizers of the dental plaque in joining the maturing community. RNA-seq analysis of S. gordonii cells in a biofilm revealed that approximately 10% of its genes are differentially expressed compared to their planktonic counterparts. Of particular interest, biofilm-derived cells upregulated SGO_2031, which encodes a putative Ne-lysine acetyltransferase, a member of the GCN5-related N-acetyltransferase (GNAT) family. Deletion of SGO_2031 causes a defect in single-species biofilm formation compared to the wild-type parent strain due to a reduction in the expression of the poly-gamma- glutamate gene (pgsA), which has been implicated in the production of extracellular polysaccharides. Our preliminary data suggest that acetylation of the sensor histidine kinase gene SGO_0299 regulates pgsA transcription and biofilm formation. This proposal will investigate the effect of SGO_0299 acetylation on its ability to phosphorylate its cognate response regulator, SGO_0298, ultimately affecting EPS production and biofilm formation. Given S. gordonii important role in oral biofilm development as an early colonizer of tooth surfaces, we will establish a murine model system to investigate how SGO_2031 dependent acetylation affects S. gordonii’s ability to colonize and shape the oral microbial community.