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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：
10662775
负责人：
Gina Lewin
金额：
$ 24.9万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-03 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10662775
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/文摘