Development and characterization of anti-P. gingivalis peptides

抗 P 的开发和表征。

• 批准号: 10625080
• 负责人: HUA XIE
• 金额: $ 14.55万
• 依托单位: MEHARRY MEDICAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625080
• 关键词: Affect; African American population; Alveolar Bone Loss; Antibiotics; Arginine deiminase; Bacteria; Binding; Biochemical; C-terminal; Cardiovascular Diseases; Cells; Chronic; Communication; Communities; Complex; Data; Dental Plaque; Development; Diabetes Mellitus; Disease; Disease Progression; Exhibits; Fimbrial Adhesins; Foundations; Genes; Genotype; Goals; Gram-Negative Bacteria; Growth; Health; Hispanic Americans; Homeostasis; Incidence; Infection; Inflammation; Inflammatory Response; Invaded; Lead; Membrane Proteins; Microbe; Microbial Biofilms; Molecular; Mus; National Health and Nutrition Examination Survey; Oral; Organism; Outcome; Pathogenesis; Pathogenicity; Patients; Peptides; Periodontal Diseases; Periodontitis; Pharmacologic Substance; Play; Population; Porphyromonas gingivalis; Predisposition; Premature Birth; Production; Receptor Signaling; Repression; Research; Role; Series; Signal Transduction; Signal Transduction Induction; Signaling Molecule; Streptococcus; Streptococcus cristatus; Streptococcus gordonii; System; Therapeutic; Therapeutic Agents; Tissues; Virulence; Virulence Factors; antagonist; caucasian American; dental biofilm; design; disease disparity; dysbiosis; genetic approach; gingipain; health disparity; in vitro Assay; in vivo; interspecies communication; microbial community; microbial host; microbiome; microorganism; mouse model; novel; oral microbial community; pathogen; peptide analog; periodontopathogen; polymicrobial biofilm; prevent; prospective; rational design; receptor; synergism

Periodontitis is the 6th most common infection worldwide and an estimated 5 – 20% of the population suffer from generalized chronic periodontitis. Studies based on the National Health and Nutrition Examination Survey (2009-2010) data demonstrated that the incidence of periodontitis is significantly higher in African Americans (AAs, 58.6%) and Hispanic Americans (HAs, 59.7%) compared to Caucasian Americans (CAs, 42.6%). Periodontitis may also have systemic health consequences leading to conditions such as cardiovascular disease, diabetes, and preterm birth, all of which are also considered disproportionally affect AAs and HAs. Microbiome is recently considered to be an important contributor to these health disparity diseases and conditions. Porphyromonas gingivalis, a gram-negative bacterium, has been recognized to play a vital role in the development of dysbiotic microbial communities and is capable of disrupting host-microbial homeostasis and inducing inflammatory responses in periodontal tissues facilitated by poly-microbes acting in concert. We recently identified a potential functional motif (SAPP), located at the C-terminal portion of S. cristatus ArcA, which can bind to surface proteins of P. gingivalis and repress the expression of fimA, mfa1 and rgps in P. gingivalis. These exciting findings provide the foundation for the proposed studies. Our overall hypothesis is that the components of the antagonistic communication system between S. cristatus and P. gingivalis can be developed to identify compounds that repress virulence factor expression and pathogenicity of P. gingivalis. The objective of this proposal is to dissect SAPP and identify the cognate P. gingivalis receptors. Therefore we will first characterize and design small peptides derived from SAPP that repress expression of virulence- associated genes in P. gingivalis. The receptor(s) of P. gingivalis that senses SAPP will then be identified and characterized. Successful completion of the proposed studies will provide fundamental novel information regarding interspecies antagonism, and could have far-reaching consequences on periodontal health by leading to discovery of potential pharmaceutical agents to inhibit P. gingivalis colonization and pathogenesis.

牙周炎是世界上第六大最常见的感染，估计有5 - 20%的人口患有牙周炎。 慢性牙周炎的症状基于国家健康和营养检查调查的研究 （2009-2010年）的数据表明，牙周炎的发病率在非洲裔美国人中明显较高， (AAs，58.6%）和西班牙裔美国人（HA，59.7%）相比，高加索美国人（CA，42.6%）。 牙周炎也可能对全身健康造成影响，导致心血管疾病等疾病。 疾病、糖尿病和早产，所有这些也被认为是对AA和HA有不良影响。 微生物组最近被认为是这些健康差异疾病的重要贡献者， 条件牙龈卟啉单胞菌是一种革兰氏阴性菌，已被认为在牙龈炎中起着至关重要的作用。 微生态失调的微生物群落的发展，并能够破坏宿主-微生物的体内平衡 并在多微生物协同作用下诱导牙周组织的炎症反应。我们 最近发现了一个潜在的功能基序（SAPP），位于S. Cristatus ArcA， 其可与牙龈卟啉单胞菌表面蛋白结合，抑制牙龈卟啉单胞菌fimA、mfa 1和rgps的表达。 牙龈炎这些令人兴奋的发现为拟议的研究提供了基础。我们的总体假设是 S. Cristatus和牙龈卟啉单胞菌可以是 开发了用于鉴定抑制牙龈卟啉单胞菌的毒力因子表达和致病性的化合物。 本提案的目的是解剖SAPP并鉴定同源牙龈卟啉单胞菌受体。因此我们 将首先表征和设计来自SAPP的抑制毒力表达的小肽- 牙龈卟啉单胞菌中的相关基因。然后将鉴定感测SAPP的牙龈卟啉单胞菌的受体， 表征了成功完成拟议的研究将提供基本的新信息 关于种间拮抗作用，并可能对牙周健康产生深远的影响， 从而发现了抑制牙龈卟啉单胞菌定殖和发病的潜在药剂。