Functional Genomics of Single- and Mixed-Species Biofilms in Spatiotemporal Scale

时空尺度上单一和混合物种生物膜的功能基因组学

• 批准号: 8727070
• 负责人: Tung T Hoang
• 金额: $ 26.79万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8727070
• 关键词: Accounting; Aleurites; Animals; Architecture; Area; Bacteria; Bacterial Physiology; Biological Models; Burkholderia; Cells; Communities; Data; Dependence; Dimensions; Disease; Equilibrium; Foundations; Gene Expression; Gene Expression Profile; Genes; Genetic; Genital system; Genomics; Goals; In Vitro; Infection; Integration Host Factors; Knowledge; Lead; Life; Lung; Microbe; Microbial Biofilms; Modeling; Molecular Genetics; Mus; Pathway interactions; Physiological; Physiology; Positioning Attribute; Process; Prokaryotic Cells; Pseudomonas; Pseudomonas aeruginosa; Publishing; Research; Resolution; Structure; Study models; Surface; System; Technology; Time; Transcript; Validation; experience; functional genomics; in vivo; in vivo Model; interest; microbiome; novel; oral bacteria; public health relevance; respiratory; single cell analysis; spatiotemporal; tool; treatment strategy

DESCRIPTION (provided by applicant): Bacteria of the oral, genital, respiratory, and gut microbiomes can exist as host- associated biofilm communities and biofilm-related infections are among the most serious diseases treated by clinicians. Bacterial associations and dynamics within the microenvironments of the biofilm structure are poorly understood on a global level. Global gene-expression dynamics of whole biofilms have been studied on the temporal scale, which lacks the resolution to decipher bacterial physiology and interactions within the microenvironments of biofilm. Thus, global gene-expression dynamics vary in two dimensions, space and time, which modulate the physiology of bacteria within their biofilm microenvironments. We have made recent advances in transcriptome analysis of single-cells have made fine-resolution functional genomic analysis of bacteria within their microenvironments possible. Our preliminary data of Pseudomonas aeruginosa (Pa) single-species biofilm has yielded many interesting aspects of this bacterium in its biofilm microenvironments and its organized spatial gene-expression pattern that make- up the living and functioning biofilm as a whole. Herein, we further proposed single- and mixed-species biofilm models of Pa and Burkholderia cenocepacia (Bc) to begin the process of unraveling the spatiotemporal global gene-expression pattern that contributes to the physiological- and interactions-dynamics of bacteria within their biofilm microenvironments. Aim 1 will determine the global gene-expression dynamics and physiology of Pa and Bc within mature single-species biofilms and Aim 2 will determine the global gene-expression dynamics, physiology, and interactions of Pa and Bc within mixed-species biofilms spatiotemporally in vitro, with validation in vivo. Upon completion of these studies, we expect to discover numerous answers to mysterious questions regarding the dynamics of bacterial physiology, interaction, and cooperation within microenvironments of single- and mixed-species biofilms at a global level. This will serve as a foundation and framework to further study the functional genomics of other host- associated biofilm communities and many important biofilm-related infections leading to novel treatment strategies.

描述（由申请人提供）：口腔、生殖器、呼吸道和肠道微生物组的细菌可以作为宿主相关的生物膜群落存在，并且生物膜相关的感染是临床医生治疗的最严重的疾病之一。在全球范围内，人们对生物膜结构微环境内的细菌关联和动态知之甚少。整个生物膜的全局基因表达动态已经在时间尺度上进行了研究，但缺乏破译细菌生理学和生物膜微环境内相互作用的分辨率。因此，全局基因表达动态在空间和时间两个维度上变化，从而调节细菌在生物膜微环境中的生理机能。我们在单细胞转录组分析方面取得了最新进展，使得对细菌微环境中的精细分辨率功能基因组分析成为可能。我们对铜绿假单胞菌（Pa）单种生物膜的初步数据已经得出了该细菌在其生物膜微环境及其组织的空间基因表达模式中的许多有趣的方面，这些模式构成了整个有生命和功能的生物膜。在此，我们进一步提出了 Pa 和新洋葱伯克霍尔德菌 (Bc) 的单种和混合物种生物膜模型，以开始解开时空全局基因表达模式的过程，该模式有助于细菌在生物膜微环境中的生理和相互作用动力学。目标 1 将确定成熟单物种生物膜内 Pa 和 Bc 的全局基因表达动态和生理学，目标 2 将在体外时空确定混合物种生物膜内 Pa 和 Bc 的全局基因表达动态、生理学和相互作用，并经过体内验证。完成这些研究后，我们期望找到关于全球范围内单一和混合物种生物膜微环境中细菌生理学动力学、相互作用和合作等神秘问题的众多答案。这将作为进一步研究其他宿主相关生物膜群落和许多重要的生物膜相关感染的功能基因组学的基础和框架，从而产生新的治疗策略。