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，例如鲍曼尼氏杆菌，会引起人类感染，但在医疗环境内部和外部花费了一部分生命周期。对这些细菌如何适应和持续在显着不同的环境中的理解非常有限。阐明环境因素以及使细菌能够在环境和医学院生活方式之间过渡的细胞和分子机制，对于理解不仅在这种过渡中起作用的基本细胞过程至关重要，而且对引起全球相关人类感染的细菌生态学作用。鲍曼尼街（A. baumannii）以抵抗抗菌剂和宿主防御能力，在不同的生态壁ches中的养分限制，在非生物和生物表面上附着并形成生物膜，抵抗确定，并持续在水，土壤，脊椎动物，脊椎动物和无蛇毒动物和不同的食物中。该细菌识别并响应各种细胞外信号，以在不同的条件和环境中持续存在。根据，我们做出了一个意想不到的新观察结果，尽管非光合合成，但鲍曼尼a。通过由BLSA介导的过程，BLSA通过未知机制使用黄素（BLUF） - 含有光感受器蛋白的短蓝色传感。基于这些观察结果，我们的中心假设是，光通过BLSA介导的过程，空间定位信号，而不是全球压力信号，这使鲍曼尼曲霉可以选择在不同环境条件下持续存在的不同生态壁cis所需的不同生活方式。该假设将通过追求三个具体目的来检验：1）确定使用分子遗传学，生物物理/生化研究和生物学测定的BLSA光感应和调节功能至关重要的结构 - 功能关系； 2）使用转录组学和蛋白质研究确定光刺激和BLSA规则的程度和组成部分； 3）使用分子遗传学，生化测定，功能测试和电子显微镜方法来表征光调节的LRPABCD伴侣/Usher Pili系统。可以预料，这项工作将为细菌感知并响应无处不在的提示（光）的机制提供新的见解，该机制标志着它们的位置，而不仅仅是引起全球压力反应，并且需要触发使用A. baumannii a. baumannii在不同环境中与非生物和生物元素相互作用。这些研究也很重要，因为它们通过打开新的途径具有积极的翻译影响，以更好地了解医疗环境和自然环境中可以用作其储层的鲍曼曼尼的生态，并更好地理解“短”光感受器，例如BLSA，例如60多个非光疗中的非弱点。