Quantitative Determination of Ecological Niches for Polymicrobial Colonization in

多种微生物定植的生态位的定量测定

• 批准号: 9193639
• 负责人: Jayajit Das
• 金额: $ 32.96万
• 依托单位: RESEARCH INST NATIONWIDE CHILDREN'S HOSP
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9193639
• 关键词: Adenoviruses; Animals; Bacteria; Child; Childhood; Chinchilla (genus); Coculture Techniques; Communities; Complex; Computer Simulation; Diagnosis; Differential Equation; Dimensions; Disease; Entropy; Goals; Heterogeneity; Homeostasis; Human; Immune; Immune response; Immune system; In Vitro; Infection; Influenza A virus; Innate Immune Response; Intervention; Investigation; Kinetics; Lead; Mathematics; Methods; Microbe; Microbial Biofilms; Modeling; Molecular; Moraxella (Branhamella) catarrhalis; Nasopharynx; Nature; Nontypable Haemophilus influenza; Organ; Organism; Otitis Media; Physics; Plant Roots; Population Dynamics; Prevention strategy; Process; Respiratory syncytial virus; Sterility; Streptococcus pneumoniae; Surface; Symbiosis; System; Therapeutic; Therapeutic Intervention; Time; Triplet Multiple Birth; Upper Respiratory Infections; Upper respiratory tract; Vaccines; Variant; Viral; Virus; Virus Diseases; adaptive immune response; base; commensal microbes; complex biological systems; computerized tools; experimental study; interdisciplinary approach; laboratory experiment; microbiota; middle ear; population based; public health relevance; response; statistics; synergism; therapeutic development; therapy development; tool; vaccine development

DESCRIPTION (provided by applicant): Quantitative determination of ecological niches for polymicrobial colonization in OM Otitis media (OM) is a common pediatric disease usually caused by polymicrobial infection of the sterile middle ear by commensal bacteria that normally reside in the upper respiratory tract (URT). OM presents a unique and simple paradigm for studying basic mechanisms of host-microbiota interactions, where breakdown of homeostasis between a small community of commensal bacteria, nontypeable H. influenzae (NTHI), S. pneumoniae (Sp), and, M. catarrhalis (Mcat), and the host's immune system by a viral infection (such as RSV or influenza A) can lead to a diseased state. The mechanisms that underlie breakdown of the homeostasis between commensal bacteria and the host are not well understood. Multiple nonlinear interlinked processes spanning a wide range of spatial dimensions (molecular to organ level) and time scales (seconds to days) determine interactions between the main players (bacteria, viruses, immune responses) involved in OM. Therefore, it is difficult to decipher the underlying mechanisms solely through experiments. We propose to use a synergistic combination of computational tools rooted in statistical physics, non-linear population dynamics, and statistics, with wet experiments in the chinchilla URT to determine and quantify ecological niches that underlie polymicrobial infection/colonization of the URT in OM. In specific aim 1, we will quantitatively determine ecological niches for infection of the chinchilla middle ear by NTHI, Sp, and Mcat. In aim 2, we will determine mechanisms underlying synergy between one virus and one type of commensal bacteria in the chinchilla URT that could lead to infection of the middle ear by the bacterial species, and in the last aim, we will determine mechanisms that lead to multispecies infection of the middle ear by Mcat and NTHI upon a synergistic viral infection.

描述（由申请人提供）：对OM耳炎培养基（OM）中多因素菌落定殖的生态壁细分的定量确定是一种常见的儿科疾病，通常是由通常驻留在上呼吸道（urt）中的，通常是由均质的中菌通过无菌中部细菌引起的。 OM presents a unique and simple paradigm for studying basic mechanisms of host-microbiota interactions, where breakdown of homeostasis between a small community of commensal bacteria, nontypeable H. influenzae (NTHI), S. pneumoniae (Sp), and, M. catarrhalis (Mcat), and the host's immune system by a viral infection (such as RSV or influenza A) can lead to病态。尚不清楚共生细菌和宿主之间体内平衡的基础的机制。多个非线性相互链接的过程涵盖了多种空间维度（分子至器官水平）和时间尺度（几秒钟至天）决定了OM涉及的主要玩家（细菌，病毒，免疫反应）之间的相互作用。因此，很难仅通过实验破译基本机制。我们建议将植根于统计物理学，非线性种群动力学和统计的计算工具的协同组合与龙猫URT中的湿实验一起确定和量化OM中urt的多数菌群感染/定植的生态壁ches。在特定的目标1中，我们将定量确定NTHI，SP和MCAT感染龙猫中耳的生态壁细分市场。在AIM 2中，我们将确定一种病毒和一种类型的共生细菌之间的机制，在龙猫urt中可能导致细菌物种感染中耳，而在最后一个目的中，我们将确定导致MCAT和NTHI的多脑感染的机制。

项目成果

Maximum Entropy Estimation of Probability Distribution of Variables in Higher Dimensions from Lower Dimensional Data.

根据低维数据对高维变量的概率分布进行最大熵估计。

• DOI: 10.3390/e17074986
• 发表时间: 2015
• 期刊: Entropy (Basel, Switzerland)
• 作者: Das,Jayajit;Mukherjee,Sayak;Hodge,SusanE
• 通讯作者: Hodge,SusanE

Host-to-host variation of ecological interactions in polymicrobial infections.

• DOI: 10.1088/1478-3975/12/1/016003
• 发表时间: 2014-12-04
• 期刊: Physical biology
• 影响因子: 2
• 作者: Mukherjee S;Weimer KE;Seok SC;Ray WC;Jayaprakash C;Vieland VJ;Swords WE;Das J
• 通讯作者: Das J