Acinetobacter baumannii gene regulation in response to illumination

鲍曼不动杆菌对光照的基因调控

• 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
• 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

 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，例如鲍曼不动杆菌，会引起人类感染，但其生命周期的一部分是在医疗环境内外度过的，但对这些细菌如何适应和在截然不同的环境中生存的了解非常有限。使细菌能够在环境生活方式和医院生活方式之间转变的细胞和分子机制对于了解在这种转变中发挥作用的基本细胞过程以及引起全球相关人类感染的细菌生态学至关重要。鲍曼不动杆菌以其抵抗抗菌剂和宿主防御的能力而闻名，在不同生态位的营养限制下能够忍受并繁衍生息，在非生物和生物表面附着并形成生物膜，抵抗干燥，并在水、土壤、脊椎动物和无脊椎动物中持续存在因此，我们相信这种细菌能够识别并响应多种细胞外信号，从而在不同的条件和环境下持续存在。新颖的观察结果是，尽管鲍曼不动杆菌不进行光合作用，但它通过差异表达生物膜形成和运动活动来感知和响应光 通过 BlsA 介导的过程，利用含有黄素 (BLUF) 结构域的光感受器蛋白进行短蓝光传感，基于这些观察结果，我们的中心假设是光通过 BlsA 介导的过程提供了一种空间定位信号，而不是全局应激信号，使鲍曼不动杆菌能够选择在不同环境条件下维持不同生态位所需的不同生活方式。该假设将通过追求三个具体目标进行检验：1）识别结构功能。使用分子遗传学、生物物理/生化研究和生物测定来确定 BlsA 光传感和调节功能的关键关系；2) 使用转录组学和蛋白质研究确定光刺激和 BlsA 调节子的程度和成分；3) 表征光调节LrpABCD 伴侣/引导菌毛系统使用分子遗传学、生化测定、功能测试和电子显微镜方法预计这项工作将为该机制提供新的见解。通过这种方式，细菌感知并响应无处不在的信号——光——发出它们的位置信号，而不仅仅是引起全局应激反应，并触发与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，使用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途径来更好地了解鲍曼不动杆菌在医疗环境和自然环境中的生态学（可以作为鲍曼不动杆菌的储存库）以及更好地了解鲍曼不动杆菌具有积极的转化影响。 “短”光感受器，例如 BlsA，可以在 60 多种非光合作用无关细菌中发挥作用。

项目成果

A Light-Regulated Type I Pilus Contributes to Acinetobacter baumannii Biofilm, Motility, and Virulence Functions.

光调节的 I 型菌毛有助于鲍曼不动杆菌生物膜、运动性和毒力功能。

• 发表时间: 2018-09
• 影响因子: 3.1
• 作者: Wood, Cecily R;Ohneck, Emily J;Edelmann, Richard E;Actis, Luis A
• 通讯作者: Actis, Luis A

The Influence of Blue Light and the BlsA Photoreceptor on the Oxidative Stress Resistance Mechanisms of Acinetobacter baumannii.

蓝光和 BlsA 光感受器对鲍曼不动杆菌氧化应激抵抗机制的影响。

• 发表时间: 2022
• 作者: Squire, Mariah S;Townsend, Hope A;Actis, Luis A
• 通讯作者: Actis, Luis A

Light Regulates Acinetobacter baumannii Chromosomal and pAB3 Plasmid Genes at 37°C.

37°C 下光调节鲍曼不动杆菌染色体和 pAB3 质粒基因。

• 发表时间: 2022-06-21
• 影响因子: 3.2
• 作者: Squire, Mariah S;Townsend, Hope A;Islam, Aminul;Actis, Luis A
• 通讯作者: Actis, Luis A

An Update on the Acinetobacter baumannii Regulatory Circuitry.

鲍曼不动杆菌调节电路的更新。

• 发表时间: 2018
• 影响因子: 15.9
• 作者: Wood, Cecily R;Mack, Lydia E;Actis, Luis A
• 通讯作者: Actis, Luis A

Structural and functional analysis of the Acinetobacter baumannii BlsA photoreceptor and regulatory protein.

鲍曼不动杆菌 BlsA 光感受器和调节蛋白的结构和功能分析。

• 发表时间: 2019
• 影响因子: 3.7
• 作者: Wood, Cecily R;Squire, Mariah S;Finley, Natosha L;Page, Richard C;Actis, Luis A
• 通讯作者: Actis, Luis A