Peptide signaling of adhesins in oral streptococci.

口腔链球菌中粘附素的肽信号传导。

• 批准号: 9404662
• 负责人: Jeffrey William Hall
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-19 至 2017-02-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9404662
• 关键词: Adhesions; Adhesives; Amino Acids; Animal Model; Antibiotic Therapy; Bacteremia; Bacteria; Bacterial Adhesins; Binding; Biological Assay; Blood Circulation; C-terminal; Cell Wall; Cell membrane; Cell surface; Cells; Charge; Cleaved cell; Complement; DNA Binding; Data; Development; Disease; Epitopes; Etiology; Extinction (Psychology); Face; Family; Fluorescence; Gel; Genes; Genetic; Genetic Transcription; Genetic study; Goals; Gram-Positive Bacteria; Growth; Human; Hydrophobicity; Immunocompromised Host; Immunologics; In Vitro; Individual; Infection; Infective endocarditis; Ligands; Mediating; Membrane; Membrane Proteins; Microbial Biofilms; Microscopy; Modeling; Molecular; Mono-S; Opportunistic Infections; Oral cavity; Organism; Pathogenicity; Peptide Signal Sequences; Peptides; Peptidoglycan; Phenotype; Phosphorylation; Phosphotransferases; Physiological; Play; Process; Property; Protein Sortings; Proteins; Proxy; Regulation; Regulon; Reporter; Reporting; Research; Risk; Role; Signal Pathway; Signal Transduction; Streptococcus Viridans Group; Streptococcus gordonii; Surface; Symbiosis; System; Testing; Therapeutic; Tissues; Transduction Gene; Up-Regulation; Work; adhesion process; base; combat; commensal microbes; experimental study; human disease; in vivo; innovation; microorganism; mutant; oral commensal; oral streptococci; pathogenic bacteria; polypeptide; polypeptide C; prevent; public health relevance; receptor; response; sensor; sensor histidine kinase; sortase; tooth surface; transcriptome

 DESCRIPTION (provided by applicant): Streptococcus gordonii is a Gram-positive oral commensal bacterium. An initial colonizer of the tooth surface, S. gordonii uses an array of adhesins to adhere and promote biofilm formation. Without these adhesins the bacterium faces extinction from the oral cavity. Upon gaining access to the bloodstream the bacterium can disseminate and adhere to host tissues resulting in opportunistic infections, namely infective endocarditis. S. gordonii readily attaches to and form biofilms on abiotic and biotic surfaces using the numerous adhesins it possesses. A family of these adhesins, termed LPXTG-motif adhesins, is important for mono- and multi-species biofilm formation on surfaces. When the processing of these adhesins is blocked or individual LPXTG-adhesins are deleted, S. gordonii senses the absence of the LPXTG-adhesins and upregulates alternative adhesins to preserve adhesion ability and biofilm formation. The upregulation of alternative adhesins is dependent on an uncharacterized, membrane-embedded, two-component signal transduction system (TCS), SGO_1180-1181. Using genetic studies, the absence of the C-terminal peptide (C-pep) of processed LPXTG-adhesins was identified as a signal for the loss of the respective adhesin. It is hypothesized that the C-peps and sensor kinase of the TCS interact in the cell membrane in a ligand/receptor partnership to sense the proper placement of LPXTG adhesins on the cell surface and regulate alternative adhesins to maintain the attachment and biofilm forming capacity of the cell. The application aims to identify and characterize the molecular interaction between C-peps and SGO_1180 and the resultant signaling cascade responsible for upregulation of alternative adhesins. Complementary in vitro and in vivo studies will characterize and determine the molecular interactions between C-peps and sensor histidine kinase, SGO_1180. Studies will investigate how the presence of C-peps influences the phospho-signaling of SGO_1180 and identify the key amino acids that mediate this interaction. Parallel studies will be conducted to identify the global regulatory impact of interactions between C-peps and SGO_1180 and identify directly regulated genes of the TCS. Ultimately, the goal is to understand the mechanism by which S. gordonii regulates adhesins and prevents eradication from the oral cavity and extinction.

 描述（由申请方提供）：戈登链球菌是一种革兰氏阳性口腔链球菌。牙齿表面的初始定殖菌为S. Gordonii使用一系列粘附素粘附并促进生物膜形成。如果没有这些粘附素，细菌将面临从口腔中灭绝的危险。一旦进入血流，细菌可以传播并粘附到宿主组织，导致机会性感染，即感染性心内膜炎。S.戈登氏菌利用其所具有的多种粘附素容易附着于非生物和生物表面并在其上形成生物膜。这些粘附素的一个家族，称为LPXTG基序粘附素，对于表面上的单物种和多物种生物膜形成是重要的。当这些粘附素的加工被阻断或单个LPXTG-粘附素被删除时，S. gordonii感觉到LPXTG-粘附素的缺乏，并上调替代粘附素以保持粘附能力和生物膜形成。替代粘附素的上调依赖于未表征的膜包埋的双组分信号转导系统（TCS）SGO_1180 - 1181。使用遗传学研究，将加工的LPXTG-粘附素的C-末端肽（C-pep）的缺失鉴定为相应粘附素损失的信号。假设TCS的C-peps和传感器激酶在细胞膜中以配体/受体伙伴关系相互作用，以感知LPXTG粘附素在细胞表面上的适当位置，并调节替代粘附素以维持细胞的附着和生物膜形成能力。该申请旨在鉴定和表征C-peps和SGO_1180之间的分子相互作用以及导致替代粘附素上调的信号级联。补充性体外和体内研究将表征和确定C-peps与传感器组氨酸激酶SGO_1180之间的分子相互作用。研究将调查C-peps的存在如何影响SGO_1180的磷酸信号传导，并确定介导这种相互作用的关键氨基酸。将进行平行研究，以确定C-peps和SGO_1180之间相互作用的全球调控影响，并确定TCS的直接调控基因。最终，目标是了解S. Gordonii调节粘附素并防止从口腔中根除和消失。