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.

项目总结/摘要 牙菌斑是人类口腔中的多微生物群落，其可导致多种牙菌斑形成。 口腔疾病与许多其他多物种微生物群落一样， 在不同的人群中，牙菌斑的空间组织相似，这表明， 支配这些社区发展的力量是保守的。链球菌 已经假设戈登氏菌在牙菌斑形成中起关键作用， 快速结合唾液涂覆的口腔表面的能力， 加入成熟的社区。RNA-seq分析S.生物膜中的戈登氏细胞显示， 大约有10%的基因与它们的同源基因相比有差异表达， 同行特别令人感兴趣的是，生物膜衍生的细胞上调SGO_2031，其编码 一种推定的N-赖氨酸乙酰转移酶，GCN 5相关N-乙酰转移酶的成员 （GNAT）家庭。SGO_2031的缺失导致单一物种生物膜形成的缺陷 与野生型亲本菌株相比，由于多聚-γ- 谷氨酸基因（pgsA），这已牵连在生产细胞外 多糖我们的初步数据表明，乙酰化的传感器组氨酸激酶， 基因SGO_0299调节pgsA转录和生物膜形成。这项建议会 研究SGO_0299乙酰化对其同源物磷酸化能力的影响 响应调节剂SGO_0298，最终影响EPS生产和生物膜形成。 给定S. gordonii作为牙齿早期定植者在口腔生物膜发育中的重要作用 表面，我们将建立小鼠模型系统，以研究SGO_2031依赖性 乙酰化作用影响S.戈登氏菌在口腔微生物群落中定殖和形成的能力。