Development and characterization of anti-P. gingivalis peptides

抗 P 的开发和表征。

基本信息

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
项目类别：
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

项目摘要

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.

牙周炎是全球第六大常见感染，估计有 5 – 20% 的人口患有牙周炎来自基于全国健康和营养检查调查的广义慢性牙周炎研究。 (2009-2010)数据显示非裔美国人牙周炎的发病率明显较高（AA，58.6％）和西班牙裔美国人（HA，59.7％）与白人美国人（CA，42.6％）相比。牙周炎还可能对全身健康产生影响，导致心血管等疾病疾病、糖尿病和早产，所有这些也被认为对 AA 和 HA 产生不成比例的影响。最近，微生物组被认为是导致这些健康差异疾病和疾病的重要因素。牙龈卟啉单胞菌是一种革兰氏阴性细菌，已被认为在其中发挥着至关重要的作用。失调微生物群落的发展，能够破坏宿主微生物稳态并在多种微生物的协同作用下诱导牙周组织的炎症反应。最近发现了一个潜在的功能基序（SAPP），位于 S. cristatus ArcA 的 C 端部分，它可以与牙龈卟啉单胞菌表面蛋白结合并抑制牙龈卟啉单胞菌中fimA、mfa1和rgps的表达。这些令人兴奋的发现为我们提出的研究奠定了基础。 S. cristatus 和 P. gingivalis 之间的拮抗通讯系统的组成部分可以是开发用于鉴定抑制牙龈卟啉单胞菌毒力因子表达和致病性的化合物。本提案的目的是剖析 SAPP 并鉴定同源牙龈卟啉单胞菌受体。将首先表征和设计源自 SAPP 的小肽，抑制毒力的表达- 然后将识别牙龈卟啉单胞菌中感知 SAPP 的受体并成功完成拟议的研究将提供基本的新颖信息。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植和发病机制的潜在药物。