The role of protein acetylation in Streptococcus gordonii biofilms

蛋白质乙酰化在戈登链球菌生物膜中的作用

• 批准号: 10527136
• 负责人: Bruno P Lima
• 金额: $ 15.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10527136
• 关键词: 16S ribosomal RNA sequencing; Acetylation; Acetyltransferase; Address; Affect; Animal Model; Bacteria; Binding; Biological Models; Biomass; Cells; Charge; Communities; Community Developments; Complex; Data; Deacetylase; Deacetylation; Defect; Dental Plaque; Development; Disease; Engineering; Family; Foundations; Genes; Genetic Transcription; Genome; Glutamates; Goals; Growth; Health; Home; Human; Human Microbiome; Human body; Laboratories; Learning; Life; Link; Luciferases; Lysine; Measures; Microbe; Microbial Biofilms; Mouth Diseases; Mus; Oral; Oral cavity; Parents; Persons; Phosphorylation; Play; Polysaccharides; Post-Translational Protein Processing; Production; Protein Acetylation; Proteins; Research; Resources; Role; Saliva; Salivary Proteins; Shapes; Streptococcus; Streptococcus gordonii; Surface; Testing; Therapeutic; Tissues; Work; amino group; base; differential expression; extracellular; genetic approach; in vivo; interest; member; microbial community; microbial composition; microbiome; microorganism; mouse model; mutant; oral bacteria; oral biofilm; oral microbial community; response; sensor histidine kinase; tooth surface; transcriptome sequencing

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.

项目摘要/摘要 牙菌斑是人口的多数群体，可以促成多个 口腔疾病。与许多其他多物种微生物群落一样，微生物也是 在不同的人中，化妆牙菌斑在空间上类似地组织，表明 管理这些社区发展的力量得到了保存。链球菌 Gordonii被认为由于其牙菌斑的发育而在牙齿发育中起着至关重要的作用 能够快速结合唾液涂层的口腔表面，以帮助牙菌斑的晚期殖民者 加入成熟社区。生物膜中Gordonii细胞的RNA-seq分析显示 与浮游物相比，其大约10％的基因表达了不同的表达 同行。特别有趣的是，生物膜衍生的单元格更新了SGO_2031，它编码 推定的Ne-赖氨酸乙酰转移酶，该乙酰基转移酶是GCN5相关的N-乙酰基转移酶的成员 （gnat）家庭。 SGO_2031的删除会导致单物种生物膜形成缺陷 与野生型母体菌株相比，由于聚-MAMA-的表达降低 谷氨酸基因（PGSA），在细胞外产生中已隐含 多糖。我们的初步数据表明传感器组氨酸激酶的乙酰化 基因SGO_0299调节PGSA转录和生物膜形成。该提议将 研究SGO_0299乙酰化对其磷酸化的能力的影响 响应调节器SGO_0298，最终影响EPS的产生和生物膜形成。 鉴于S. gordonii在口服生物膜发育中的重要作用，作为早期牙齿的菌落器 表面，我们将建立一个鼠模型系统，以研究如何依赖SGO_2031 乙酰化影响S. gordonii殖民和塑造口腔微生物群落的能力。