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: 10284137
• 负责人: Gina Lewin
• 金额: $ 11.99万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284137
• 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; 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

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.

项目摘要/摘要 链球菌是人口腔中最丰富的微生物，大多数人都有多个 物种，通常是同一物种的多种菌株（1-6）。此外，大多数口服 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（例如卟啉单胞菌（PG））的物理位置和毒力因子表达， 聚集的放线菌菌（AA）和核细菌核（2，3，7-11）。这些相互作用 影响疾病的进展和严重程度及其对治疗的抵抗力（7，12-16）。然而， 这些相互作用也依赖于已知在整个属中变化的特征，例如细胞 表面结构和分泌有机酸（17、18）。此外，转录异质性导致 亚群的存在，可以进一步改变链球菌的行为（19-23）。因此，虽然丰富 链球菌属被认为是病原体行为的重要介体，尚不清楚如何了解 链球菌 - 病原体相互作用在属的基因组和转录组多样性中各不相同。在这个 研究，总体假设是共生的基因组，表型和转录异质性 链球菌改变了与病原体的相互作用并影响感染。该建议旨在扩大我们的 通过研究两个级别的多样性：基因组和 转录。首先，它建议系统地表征分类学上多样的相互作用 链球菌与病原体Pg和AA在系统基因框架中（AIM 1）。这项工作将确定规模 在链球菌属中相互作用变化，并可能识别介导的新功能 与这些病原体的相互作用。其次，该建议将表征转录异质性 共生链球菌导致亚群，并询问亚群的影响，并受到影响 通过，与口腔病原体的相互作用（AIM 2）。这个目标将大大提高我们对 口服共生链球菌中的转录异质性，分类法的变化以及如何改变 通过环境变化。此外，这两个目标都将考虑链球菌多样性的相互作用和 在微观级别的空间图案上的相互作用。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。