权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Probing the role of heterogeneity in streptococcal interactions

探讨异质性在链球菌相互作用中的作用

基本信息

批准号：
10456196
负责人：
Gina Lewin
金额：
--
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2022-08-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10456196
关键词：
Abscess Actinobacillus actinomycetemcomitans Address Animal Model Area Behavior Cell surface Cells Communities Complex Development Disease Disease Outcome Disease Progression Fusobacterium nucleatum Gene Expression Gene Expression Profile Genes Genetic Genetic Transcription Genomics Genotype Goals Grant Health Health Promotion Heterogeneity Human Hydrogen Peroxide In Vitro Infection Laboratories Location Measures Mediating Mediator of activation protein Microbe Microscopy Modeling Mouth Diseases Mus Oral Oral cavity Pattern Periodontitis Persons Phenotype Physiology Population Porphyromonas gingivalis Production Research Research Personnel Resistance Role Severity of illness Shapes Spatial Distribution Streptococcus Streptococcus adhesin Structure Taxonomy Testing Training Variant Virulence Factors Work base commensal bacteria environmental change gain of function improved innovation loss of function member mutant novel strategies oral behavior oral commensal oral microbial community oral pathogen oral streptococci organic acid pathogen receptor single-cell RNA sequencing small molecule trait transcriptomics

项目摘要

PROJECT SUMMARY/ABSTRACT Streptococci are the most abundant microbes in the human oral cavity, with most people harboring multiple species, and often even multiple strains of the same species (1-6). Further, while most species of oral streptococci are not pathogenic, studies with selected strains have shown that streptococci can influence the physical location and the virulence factor expression of oral pathogens such as Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans (Aa), and Fusobacterium nucleatum (2, 3, 7-11). These interactions influence the progression and severity of disease, as well as its resistance to treatment (7, 12-16). However, these interactions also rely are governed by the traits that are known to vary across the genus, such as cell surface structures and secreted organic acids (17, 18). Further, transcriptional heterogeneity resulting in the existence of subpopulations, can further alter the behavior of streptococci (19-23). Thus, while the abundant streptococcal genus is thought of as an important mediator of pathogen behavior, it is not well understood how streptococcal-pathogen interactions vary across the genomic and transcriptomic diversity of the genus. In this study, the overarching hypothesis is that genomic, phenotypic, and transcriptional heterogeneity of commensal streptococci alters interactions with pathogens and impacts infections. This proposal aims to expand our understanding of streptococcal-pathogen interactions by investigating diversity at two levels: genomic and transcriptional. First, it proposes to systematically characterize the interactions formed by taxonomically diverse streptococci with the pathogens Pg and Aa in a phylogenomic framework (Aim 1). This work will identify the scale at which interactions vary across the streptococcal genus and potentially identify new functions that mediate interactions with these pathogens. Second, this proposal will characterize the transcriptional heterogeneity in commensal streptococci that result in subpopulations and ask how subpopulations influence, and are influenced by, interactions with oral pathogens (Aim 2). This aim will significantly advance our understanding of the role of transcriptional heterogeneity in oral commensal streptococci, how it varies taxonomically, and how it is altered by environmental changes. Further, both Aims will consider the interplay of streptococcal diversity and interactions on spatial patterning at the micron-level. Overall, the proposed research will broaden our understanding of the role of streptococci during oral disease.

项目总结/摘要链球菌是人类口腔中最丰富的微生物，大多数人携带多种链球菌。物种，甚至经常是同一物种的多个菌株（1-6）。此外，虽然大多数物种的口腔链球菌不是致病性的，对选定菌株的研究表明，链球菌可以影响口腔病原体如牙龈卟啉单胞菌（Pg）的物理位置和毒力因子表达， Aggregatibacteractinomycetemcomitans（Aa）和具核梭杆菌（Fusobacteriumnucleatum）（2，3，7-11）。这些相互作用影响疾病的进展和严重程度，以及对治疗的抵抗力（7，12-16）。然而，在这方面，这些相互作用还依赖于已知在属间变化的性状，如细胞表面结构和分泌的有机酸（17，18）。此外，转录的异质性导致了基因组的突变。亚群的存在可进一步改变链球菌的行为（19-23）。虽然，链球菌属被认为是病原体行为的重要媒介，但其如何作用还不清楚。链球菌-病原体相互作用在该属的基因组和转录组多样性中变化。在这研究中，首要的假设是，基因组，表型和转录异质性，链球菌改变与病原体的相互作用并影响感染。这项建议旨在扩大我们的通过调查两个水平的多样性来了解链球菌-病原体相互作用：基因组和转录的首先，它建议系统地描述由分类多样性形成的相互作用，链球菌与病原体Pg和Aa的基因组框架（Aim 1）。这项工作将确定规模在该水平上，链球菌属之间的相互作用各不相同，并可能确定介导与这些病原体的相互作用。第二，这项建议将描述转录异质性，导致亚群的链球菌，并询问亚群如何影响，与口腔病原体的相互作用（目的2）。这一目标将极大地促进我们对口腔链球菌的转录异质性，它在分类学上如何变化，以及它是如何改变的环境的变化。此外，两个目标都将考虑链球菌多样性的相互作用，在微米级的空间图案的相互作用。总体而言，拟议的研究将扩大我们的了解链球菌在口腔疾病中的作用。