Regulation of gtf Gene Expression in S mutans

变形链球菌中 gtf 基因表达的调控

• 批准号: 6918548
• 负责人: STEVEN D GOODMAN
• 金额: $ 26.45万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918548
• 关键词: Streptococcus mutans; bacteria infection mechanism; bacterial genetics; dental agent; dental caries; gene deletion mutation; gene expression; genetic promoter element; genetic regulation; genetic regulatory element; genetic transcription; glucans; hexosyltransferase; messenger RNA; northern blottings; phenotype; plasmids; polymerase chain reaction; regulatory gene; reporter genes; transposon /insertion element

Streptococcus mutans is a causative agent of dental caries. It's ability to inflict damage is strongly linked to the production of long chain glucose polymers (glucans) derived from dietary sucrose which allow the bacteria possesses a family of genes that express enzymes called glucosyltransferases (GTF). There are three GTFs in S. mutans. They share 50 percent sequence identity and are encoded by the homologous gtfB, gtfC and gtfD genes. The gtfB and gtfC gene are found in direct repeat with a mere 198 base paries separation between coding sequences. Although mutations in either gtfB or gtfC produce a colonizing deficient phenotype, little is known about their regulation. Until recently, the only effector known to regulate these genes was sucrose, the substrate of the GTFs. Supplemented sucrose transiently induces a 3-fold increase in a gtfB transcriptional fusion. Now we have demonstrated that both gtfB and gtfC show coordinated growth phase- dependent expression. For both genes, expression peaks prior to exponential growth and falls over 100-fold by early stationary phase. In this proposal, we intend to further study this phenomenon including identifying critical cis and trans acting elements and through mutagenesis determine how these elements affect gtf gene expression. Since these gtf genes are involved in the colonization process, the genetic elements that are found here will need to be examined in terms of the bacteria's pathogenic mechanisms.

变形链球菌是龋齿的病原体。 它造成损害的能力与源自膳食蔗糖的长链葡萄糖聚合物（葡聚糖）的产生密切相关，这使得细菌拥有一系列表达称为葡萄糖基转移酶（GTF）的酶的基因。 变形链球菌中有 3 个 GTF。 它们具有 50% 的序列同一性，并由同源 gtfB、gtfC 和 gtfD 基因编码。 gtfB 和 gtfC 基因被发现直接重复，编码序列之间仅间隔 198 个碱基对。尽管 gtfB 或 gtfC 的突变会产生定植缺陷表型，但人们对它们的调节知之甚少。 直到最近，已知唯一能调节这些基因的效应物是蔗糖，它是 GTF 的底物。补充蔗糖可短暂诱导 gtfB 转录融合增加 3 倍。 现在我们已经证明 gtfB 和 gtfC 都显示出协调的生长阶段依赖性表达。 对于这两个基因，表达在指数增长之前达到峰值，并在稳定期早期下降 100 倍以上。 在本提案中，我们打算进一步研究这一现象，包括识别关键的顺式和反式作用元件，并通过诱变确定这些元件如何影响 gtf 基因表达。 由于这些 gtf 基因参与定植过程，因此需要根据细菌的致病机制对此处发现的遗传元件进行检查。

项目成果

Dissecting the Role of VicK Phosphatase in Aggregation and Biofilm Formation of Streptococcus mutans.

剖析 VicK 磷酸酶在变形链球菌聚集和生物膜形成中的作用。

• 发表时间: 2021
• 影响因子: 7.6
• 作者: Wang, S;Long, L;Yang, X;Qiu, Y;Tao, T;Peng, X;Li, Y;Han, A;Senadheera, D B;Downey, J S;Goodman, S D;Zhou, X;Cvitkovitch, D G
• 通讯作者: Cvitkovitch, D G