Unearthing interacting nontuberculous mycobacterial, environmental, and host determinants of lung disease in the Hawai'i Islands

这项研究将研究环境因素对一种自然发生的细菌--非结核分枝杆菌（NTM）的影响，这种细菌会引起人类的一种传染性肺病。它发生在地球仪和受影响的人数正在增加;它感染18万人在美国每年。夏威夷是美国这种肺病发病率最高的地区。虽然NTM被认为是一种环境获得性细菌，但我们对它们生活在环境中的位置有很多不了解，其中哪些地方对进入人体并引起疾病最重要，以及与宿主的相互作用如何引起疾病。这个跨学科的项目将研究从广泛的环境中发现的NTM，如家庭水源、土壤、野猪和健康人，并将这些与来自夏威夷患者的菌株进行比较。这将是第一次在一个模型中同时研究土壤和水特征、气候因素、人类基因和行为、细菌基因组学以及潜在的脊椎动物水库。这项工作将帮助我们了解有时自由生活，有时与人和动物相关的细菌如何利用其环境，并提供有关环境获得性NTM肺病的必要信息，以及如何减少这些类型的感染。这项研究将涉及一个大规模的公民科学项目。它将让患者参与研究，建立外展计划，并指导来自夏威夷和其他代表性不足的太平洋岛屿的高中生，本科生和研究生以及博士后研究员在微生物学，微生物基因组学和生态学以及数学建模领域。这将有助于减少和消除难以治疗的NTM infections.This study will investigate environmental and clinical nontuberculous mycobacteria（NTM）by comprehensive characterizing genomic signatures of these opportunistic pathogens，and identifying where they resident in the environment.将通过对NTM肺病患者的基因组进行测序来检查人类对NTM感染的易感性，以调查和确定影响疾病发生率的人类遗传因素，包括检查免疫基因、纤毛功能基因和影响身体或器官形态的基因。将对来自夏威夷的3,000多个环境样本进行检查，并对1,000多个环境和临床NTM细菌菌株进行全基因组测序，以全面表征夏威夷群岛上临床相关NTM物种的基因组进化和种群动态。这些数据将与水和土壤特征的环境分析相结合，以确定有助于NTM在环境中生存和定植的变量。通过对个人获得NTM感染的建模，该研究将有助于确定特定的环境，气候，动物水库，宿主遗传异常和行为，以及促进这种收购的特定遗传亚型，从而推动夏威夷NTM肺病的高患病率。因此，这项研究将揭示影响环境获得性病原体宿主定殖的生态过程。

This research will study the environmental factors affecting a naturally occurring type of bacteria, nontuberculous mycobacteria (NTM), which cause an infectious type of lung disease in people. It occurs around the globe and number of people affected is increasing; it infects 180,000 people in the United States each year. Hawaii has the highest prevalence of this lung disease in the United States. While NTM are regarded as an environmentally acquired type of bacteria, there is much we don't understand about where they live in the environment, which of those places are most important for getting into people and causing disease, and how interactions with the host cause disease. This interdisciplinary project will study NTM found from a broad range of environments, such as household water sources, soils, feral pigs, and healthy humans, and compare these to strains from patients in Hawaii. This will be the first time soil and water characteristics, climatic factors, human genes and behaviors, bacterial genomics, and potential vertebrate reservoirs are studied together in a single model. The work will help us understand how bacteria that are sometimes free living and sometimes associated with people and animals use their environment, and provide needed information about environmentally acquired NTM lung disease, and how to reduce these types of infections. This research will involve a large-scale citizen science project. It will involve patients in research, establish outreach programs, and mentor high school, undergraduate, and graduate students, and postdoctoral fellows from Hawaii and other underrepresented Pacific Islands in the fields of microbiology, microbial genomics and ecology, and mathematical modeling. It will contribute to the goal of reducing and perhaps eliminating difficult-to-treat NTM infections.This study will investigate environmental and clinical nontuberculous mycobacteria (NTM) by comprehensively characterizing genomic signatures of these opportunistic pathogens, and identifing where they reside in the environment. Human susceptibility to NTM infections will be examined by sequencing the genomes of individuals with NTM lung disease, to investigate and identify human genetic factors influencing disease incidence, including the examination of immune genes, cilia function genes, and genes affecting body or organ morphology. Over 3,000 environmental samples from Hawaii will be examined, and whole genome sequencing of over 1,000 environmental and clinical NTM bacterial strains will be conducted to comprehensively characterize the genome evolution and population dynamics of clinically relevant NTM species on the Hawaiian islands. These data will be combined with environmental analysis of water and soil characteristics to identify variables contributing to NTM survival and colonization in the environment. Through modeling of where individuals acquire NTM infections the research will contribute to identifying specific environmental, climatological, animal reservoirs, host genetic anomalies and behaviors, and particular genetic subtypes that facilitate this acquisition, driving the high prevalence of NTM lung disease in Hawaii. The research will thereby shed light on ecological processes affecting host colonization by environmentally acquired pathogens.