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

• 批准号: 10841244
• 负责人: Gina Lewin
• 金额: $ 11.2万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-08 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10841244
• 关键词: Abscess; Actinobacillus actinomycetemcomitans; Animal Model; Behavior; Cell surface; Cells; Coculture Techniques; Communities; Complex; Development; Disease; Disease Outcome; Disease Progression; Environment; Fusobacterium nucleatum; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Genomics; Genotype; Goals; Grant; Health; Health Promotion; Heterogeneity; Human; Hydrogen Peroxide; In Vitro; Infection; Location; Measures; Mediating; Mediator; Microbe; Modeling; Mouth Diseases; Mus; Oral; Oral cavity; Pattern; Periodontitis; Persons; Phenotype; Physiology; Population; Porphyromonas gingivalis; Production; Research; Resistance; Role; Severity of illness; Shapes; Spatial Distribution; Streptococcus; Streptococcus adhesin; Structure; Taxonomy; Testing; Universities; Variant; Virulence Factors; Work; commensal bacteria; environmental change; gain of function; improved; innovation; loss of function; mutant; novel strategies; oral bacteria; oral behavior; oral commensal; oral microbial community; oral pathogen; oral streptococci; organic acid; pathogen; professor; receptor; small molecule; trait; transcriptomics

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 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, which results in subpopulations, can further alter the behavior of microbes (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 are impacted by genomic and transcriptomic diversity. In this study, the overarching hypothesis is that genomic, phenotypic, and transcriptional heterogeneity impacts the interactions between commensal streptococci and oral pathogens, and impacts infection. This grant aims to expand our understanding of streptococcal-pathogen interactions by investigating diversity at two levels: genomic and transcriptional. First, it will 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 grant will characterize the transcriptional heterogeneity in commensal streptococci that result in subpopulations and ask how streptococcal-pathogen interactions influence, and are influenced by, subpopulations (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, this research will broaden our understanding of the role of streptococci during oral disease.

项目概要/摘要 链球菌是人类口腔中最丰富的微生物，大多数人都携带多种链球菌。 物种，通常甚至是同一物种的多个菌株 (1-6)。此外，虽然大多数物种的口腔 链球菌不具有致病性，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， 伴放线聚集杆菌 (Aa) 和具核梭杆菌 (2, 3, 7-11)。这些互动 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， 这些相互作用也受到已知在不同属中不同的特征的控制，例如细胞表面 结构和分泌的有机酸 (17, 18)。此外，转录异质性导致 亚群，可以进一步改变微生物的行为 (19-23)。因此，虽然丰富的链球菌属 链球菌被认为是病原体行为的重要介质，但目前尚不清楚链球菌如何 病原体相互作用受到基因组和转录组多样性的影响。在这项研究中，总体 假设是基因组、表型和转录异质性影响之间的相互作用 共生链球菌和口腔病原体，并影响感染。这笔赠款旨在扩大我们的理解 通过研究基因组和转录两个水平的多样性来研究链球菌-病原体相互作用。第一的， 它将系统地描述分类学上多样化的链球菌与 系统发育框架中的病原体 Pg 和 Aa（目标 1）。这项工作将确定互动的规模 链球菌属之间存在差异，并可能识别介导与这些链球菌属相互作用的新功能 病原体。其次，这项资助将表征共生链球菌的转录异质性， 产生亚群，并询问链球菌-病原体相互作用如何影响，以及受以下因素影响： 亚人群（目标 2）。这一目标将显着增进我们对转录作用的理解 口腔共生链球菌的异质性、其分类学上的变化以及环境如何改变它 变化。此外，这两个目标都将考虑链球菌多样性的相互作用以及空间上的相互作用。 微米级的图案化。总的来说，这项研究将拓宽我们对链球菌作用的理解 口腔疾病期间。