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: 10673091
• 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/10673091
• 关键词: 16S ribosomal RNA sequencing; Acetylation; Acetyltransferase; Address; Adsorption; 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; 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.

项目概要/摘要 牙菌斑是人类口腔中的多种微生物群落，可导致多种微生物的产生。 口腔疾病。与许多其他多物种微生物群落一样，这些微生物 不同人的牙菌斑在空间上的组织方式相似，这表明 支配这些社区发展的力量得到了保存。链球菌属 据推测，gordonii 在牙菌斑的形成中发挥着至关重要的作用，因为它 快速结合唾液覆盖的口腔表面的能力，有助于牙菌斑的晚期定殖 加入成熟的社区。生物膜中戈登沙门氏菌细胞的 RNA-seq 分析揭示 与浮游生物相比，其大约 10% 的基因存在差异表达 同行。特别令人感兴趣的是，生物膜衍生细胞上调了 SGO_2031，该细胞编码 推定的 Ne-赖氨酸乙酰转移酶，GCN5 相关 N-乙酰转移酶的成员 （GNAT）家族。 SGO_2031的删除导致单物种生物膜形成缺陷 与野生型亲本菌株相比，由于多聚γ-的表达减少 谷氨酸基因（pgsA），与细胞外物质的产生有关 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。该提案将 研究 SGO_0299 乙酰化对其同源物磷酸化能力的影响 反应调节剂 SGO_0298，最终影响 EPS 生产和生物膜形成。 鉴于戈登沙门氏菌作为牙齿的早期定植者，在口腔生物膜发育中发挥重要作用 表面，我们将建立一个小鼠模型系统来研究SGO_2031如何依赖 乙酰化会影响戈登沙门氏菌定植和塑造口腔微生物群落的能力。