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Acinetobacter baumannii gene regulation in response to illumination

鲍曼不动杆菌对光照的基因调控

基本信息

批准号：
9017300
负责人：
Luis A Actis
金额：
$ 35.98万
依托单位：
MIAMI UNIVERSITY OXFORD
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-18 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9017300
关键词：
Acinetobacter Acinetobacter baumannii Adherence Adopted Affect Amino Acids Animals Bacteria Biochemical Biogenesis Biological Assay Cell physiology Complex Cues Data Desiccation Ecology Electron Microscopy Elements Environment Environmental Risk Factor Flavins Food Gene Expression Regulation Genetic Goals Health Host Defense Human Infection Invertebrates Knowledge Life Cycle Stages Life Style Light Lighting Location Mediating Medical Methods Microbial Biofilms Modeling Molecular Molecular Chaperones Molecular Genetics Nature Nosocomial Infections Nutrient Outcome Output Pathway interactions Photoreceptors Photosens Physiology Pilum Play Process Property Proteins Regulon Reporting Research Role Sampling Signal Transduction Signal Transduction Pathway Site Soil Source Stress Structure Structure-Activity Relationship Surface System Testing Water Work antimicrobial drug base biological adaptation to stress cell motility differential expression extracellular insight member novel public health relevance response transcriptomics

项目摘要

DESCRIPTION (provided by applicant) Some bacteria, such as Acinetobacter baumannii, cause human infections but spend portions of their life cycles both inside and outside medical settings. The understanding of how these bacteria adapt to and persist in significantly different environments is very limited. The elucidation of the environmental factors and the cellular and molecular mechanisms that enable bacteria to transition between environmental and nosocomial lifestyles is critical for understanding not only basic cellular processes that play a role in this transition, but also the ecology of bacteria that cause relevant human infections worldwide. A. baumannii is known for its capacity to resist antimicrobial agents and host defenses, endure and prosper under nutrient limitation in different ecological niches, attach to and form biofilms on abiotic and biotic surfacs, resist desiccation, and persist in water, soil, vertebrate and invertebrate animals and different food sources. Thus, we believe that this bacterium recognizes and responds to a wide range of extracellular signals to persist under different conditions and environments. Accordingly, we made the unexpected and novel observation that, although non- photosynthetic, A. baumannii senses and responds to light by differentially expressing biofilm formation and motility activities through a process mediated by BlsA, a short blue-light sensing using flavin (BLUF)-domain- containing photoreceptor protein, by unknown mechanisms. Based on these observations, our central hypothesis is that light provides, through a BlsA-mediated process, a spatial localization signal, rather than a global stress signal, which allows A. baumannii to choose different lifestyle needed to persist in distinct ecological niches under different environmental conditions. This hypothesis will be tested by pursuing three specific aims: 1) Identify structure-function relationships critical for BlsA light-sensing and regulatory functions using molecular genetics, biophysical/biochemical studies and biological assays; 2) Determine the extent and components of the light stimulon and BlsA regulon using transcriptomics and protein studies; and 3) Characterize the light-regulated LrpABCD chaperone/usher pili system using molecular genetics, biochemical assays, functional tests and electron microscopy methods. It is anticipated that this work will provide novel insights into the mechanisms by which bacteria sense and respond to a ubiquitous cue - light - that signals their location, rather than only causing a global stress reaction, and triggers responses needed to interact with abiotic and biotic elements found in different environments using A. baumannii as a working model. These studies are also significant since they have a positive translational impact by opening new avenues to better understand the ecology of A. baumannii in medical settings and the natural environment, which could serve as its reservoir, as well as to better understand "short" photoreceptors such as BlsA, which could be active in more than 60 non-photosynthetic unrelated bacteria.

描述（由申请人提供）一些细菌，如鲍曼不动杆菌，会引起人类感染，但它们的生命周期的一部分都是在医疗环境内外度过的。对这些细菌如何适应并在显著不同的环境中持续存在的理解非常有限。阐明环境因素以及使细菌能够在环境和医院生活方式之间转变的细胞和分子机制，不仅对于理解在这种转变中发挥作用的基本细胞过程至关重要，而且对于理解导致全球相关人类感染的细菌生态也至关重要。A.鲍曼不动杆菌以其抵抗抗微生物剂和宿主防御的能力、在不同生态环境中在营养限制下的耐受性和繁殖能力、附着于非生物和生物表面并在其上形成生物膜的能力、抗干燥的能力以及在水、土壤、脊椎动物和无脊椎动物以及不同食物来源中的持久性而闻名。因此，我们认为这种细菌识别并响应广泛的细胞外信号，以在不同的条件和环境下持续存在。因此，我们做了意想不到的和新颖的观察，虽然非光合作用，A.鲍曼不动杆菌通过差异表达生物膜形成和运动活性来感知和响应光通过BlsA介导的过程，BlsA是一种使用含有黄素（BLUF）结构域的光感受器蛋白的短蓝光感测，其机制未知。基于这些观察，我们的中心假设是，光通过BlsA介导的过程提供了空间定位信号，而不是全局应力信号，这使得A.鲍曼不动杆菌选择不同的生活方式需要在不同的环境条件下坚持不同的生态位。该假说将通过以下三个具体目标进行验证：1）利用分子遗传学、生物物理/生物化学研究和生物学测定来确定BlsA光传感和调节功能的关键结构-功能关系; 2）利用转录组学和蛋白质研究来确定光刺激子和BlsA调节子的范围和组成;和3）利用分子遗传学、生物化学测定、功能测试和电子显微镜方法表征光调节LrpABCD伴侣/引导皮利系统。预计这项工作将为细菌感知和响应无处不在的线索-光-的机制提供新的见解，光发出它们的位置信号，而不仅仅是引起全球应激反应，并触发与使用A在不同环境中发现的非生物和生物元素相互作用所需的反应。鲍曼不动杆菌作为工作模型。这些研究也很重要，因为它们通过开辟新的途径来更好地了解A.在医疗环境和自然环境中的鲍曼不动杆菌，这可以作为其水库，以及更好地了解“短”光感受器，如BlsA，它可以在60多个非光合无关的细菌活性。