Binding specificity and transcriptional regulation of antigen I/II adhesins in Streptococcus gordonii

项目摘要/摘要 细菌表达细胞表面相关的粘附素蛋白有助于生物膜的形成。牙科 菌斑是人类口腔的一种多菌生物膜，会导致口腔传染病。形成 这种牙科生物膜是由先驱定植启动的，链球菌利用粘附素蛋白 附着在唾液覆盖的牙齿表面。在链球菌表达的众多粘附素中，抗原型 I/II(agi/II)黏附素家族是一个广泛保守的家族，在多种宿主间的相互作用中发挥着重要作用 分子和其他口腔微生物。这项建议使用戈登链球菌作为模型来研究其作用。 AgI/II黏附素在宿主表面附着和生物膜发育中的作用。S.gordonii是一种口头共生， 表达两种AgI/II黏附素：SSPA和SspB(SSPA/B)。有证据表明，中学学位分配办法/B是必要的 附着在唾液粘蛋白5B(MUC5B)涂层表面。拟议的实验将研究结合 SSPA/B蛋白和MUC5B多聚糖之间的差异。SSPA和SspB的可变(V)区预计将 以不同的方式结合装饰MUC5B肽骨架的O-葡聚糖，有助于初始附着。 然而，随着生物膜的成熟，SSPA/B的表达减少，这表明转录调控 SSPA/B很复杂。数据表明，在最初的表面附着后，蛋白质乙酰化调节sspAB 通过双组分系统BfrAB进行表达。因此，遗传方法被提出用来研究 蛋白质乙酰化在SSPA/B基因转录中的作用总体而言，这些研究将表明戈登氏链球菌agi/II 粘附素介导与MUC5B的结合，并通过BFRB传感器激酶的乙酰化在转录上进行调节。 研究结果可能广泛适用于链球菌AgI/II粘附素，并可能提出新的机制来 在健康和链球菌疾病中控制微生物群落的发展。

Project Summary/Abstract Bacterial expression of cell surface-associated adhesin proteins facilitates the formation of biofilms. Dental plaque is a polymicrobial biofilm of the human mouth that contributes to oral infectious diseases. Formation of this dental biofilm is initiated by pioneer colonization, whereby Streptococcus species use adhesin proteins to attach to the saliva-coated tooth surface. Among the many adhesins expressed by Streptococci, the antigen type I/II (AgI/II) adhesin family is widely conserved and has been shown to mediate interactions with several host molecules and other oral microbes. This proposal uses Streptococcus gordonii as a model to investigate the role of AgI/II adhesins in host surface attachment and biofilm development. S. gordonii is an oral commensal that expresses two AgI/II adhesins: SspA and SspB (SspA/B). Evidence shows that SspA/B is necessary for attachment to salivary mucin 5B (MUC5B)-coated surfaces. Proposed experiments will investigate binding between SspA/B proteins and MUC5B glycans. The variable (V) regions of SspA and SspB are expected to differentially bind the O-glycans decorating the MUC5B peptide backbone, contributing to initial attachment. SspA/B expression decreases, however, as the biofilm matures, suggesting that transcriptional regulation of sspA/B is complex. Data suggests that after initial surface attachment, protein acetylation regulates sspAB expression via the two-component system BfrAB. Therefore, genetic approaches are proposed to investigate the role of protein acetylation in sspA/B gene transcription. Overall, these studies will show that S. gordonii AgI/II adhesins mediate binding to MUC5B and are transcriptionally regulated by acetylation of the BfrB sensor kinase. Findings may be broadly applicable to streptococcal AgI/II adhesins and may suggest new mechanisms to control microbial community development in health and in streptococcal disease.