Protein exchange and self recognition in myxobacteria biofilms

粘细菌生物膜中的蛋白质交换和自我识别

• 批准号: 8274042
• 负责人: DANIEL WALL
• 金额: $ 26.89万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8274042
• 关键词: Accounting; Animal Model; Antibiotics; Binding; Biological; Biomedical Research; Cell Communication; Cell Surface Receptors; Cell physiology; Cells; Chimeric Proteins; Communication; Complement; Complex; Cooperative Behavior; Development; Eukaryotic Cell; Fruit; Genetic; Genetic Determinism; Gram-Negative Bacteria; Homeostasis; Immune system; Infection; Intervention; Knowledge; Lead; Light; Lipoproteins; Liquid substance; Location; Mediating; Medical; Membrane; Membrane Fusion; Membrane Lipids; Microbe; Microbial Biofilms; Modeling; Molecular; Movement; Myxococcales; Myxococcus xanthus; Nanotubes; Pathway interactions; Phenotype; Play; Process; Proteins; Resistance; Resource Sharing; Role; Site; Social Interaction; Specificity; Structure; Surface; Swimming; System; Testing; Work; antimicrobial drug; base; improved; killings; microbial; microbial community; novel; social

DESCRIPTION (provided by applicant): Biofilms are surface attached microbial communities that predominates infection sites, and are of keen medical importance as they resist killing by antibiotics and the immune system. Progress in understanding how biofilm cells interact to elicit phenotypic changes has been impeded by limited strategies to probe their cellular interactions. Here, we seek to fill-in knowledge gaps by describing a novel process where cells within biofilms exchange their outer membrane (OM) lipoproteins, which result in phenotypic changes. Our model organism, Myxococcus xanthus, is a social gram-negative bacterium that can undergo multicellular development, is used to probe biofilm cellular dynamics. In preliminary results we now show that OMs are also exchanged and we identify cellular proteins required for transfer. We also show that transfer, which only occurs in structured biofilms, involves kin recognition whereby cells distinguish themselves from other closely related M. xanthus isolates. As transfer involves costly bulk movement of OM material, we believe this exchange process is a form of cooperative behavior where cells communicate and share resources. Lastly, we show transfer regulates swarm expansion and may be mediated by nanotube structures. Our results have broad implications as eukaryotic cells are widely known to exchange cellular components, and in bacterial systems, protein exchange is beginning to be appreciated as a prevalent process involved in communication and diverse cellular processes. Our genetic system is well poised to tackle these fundamental issues. Here, in Aim 1 we will use genetic approaches to identify the cellular complement of proteins involved in transfer, and define their interactions an the role nanotubes might play in transfer. Aim 2 will characterize the mechanism of kin recognition in transfer and define the genetic determinant for cell-cell recognition. Aim 3 will determine how OM exchange regulates swam expansion and a role it might play in development and envelope homeostasis. These combined efforts will advance our mechanistic understanding of how biofilm cells interact, recognize one another and exchange cellular material, which results in phenotypic changes that are distinct from planktonic or isolated cells. PUBLIC HEALTH RELEVANCE: Biofilms are dense microbial mats that are medically important as they account for most microbial infections. Biofilm infections are difficult and expensive to treat because they are resistant to the host immune system and antimicrobial agents. This proposal seeks to investigate novel cell interactions in biofilms, which may advance our understanding of biofilms and consequently lead to improved intervention strategies.

描述（由申请人提供）：生物膜是表面附着的微生物群落，在感染部位占主导地位，并且具有重要的医学重要性，因为它们可以抵抗抗生素和免疫系统的杀伤。探索生物膜细胞相互作用的策略有限，阻碍了理解生物膜细胞如何相互作用以引起表型变化的进展。在这里，我们试图通过描述一种新的过程来填补知识空白，在该过程中，生物膜内的细胞交换其外膜（OM）脂蛋白，从而导致表型变化。我们的模型生物黄粘球菌是一种社会性革兰氏阴性细菌，可以进行多细胞发育，用于探测生物膜细胞动力学。在初步结果中，我们现在表明 OM 也发生了交换，并且我们鉴定了转移所需的细胞蛋白。我们还表明，仅发生在结构化生物膜中的转移涉及亲缘识别，从而使细胞将自己与其他密切相关的 M. xanthus 分离株区分开来。由于转移涉及 OM 材料的昂贵的批量移动，我们认为这种交换过程是细胞通信和共享资源的一种合作行为形式。最后，我们表明转移调节群体扩张，并可能由纳米管结构介导。我们的结果具有广泛的意义，因为众所周知，真核细胞可以交换细胞成分，并且在细菌系统中，蛋白质交换开始被认为是参与通讯和多种细胞过程的普遍过程。我们的遗传系统已经做好了解决这些基本问题的准备。在这里，在目标 1 中，我们将使用遗传方法来识别参与转移的蛋白质的细胞补体，并定义它们的相互作用以及纳米管在转移中可能发挥的作用。目标 2 将描述转移中亲属识别的机制，并定义细胞间识别的遗传决定因素。目标 3 将确定 OM 交换如何调节群体扩张及其在发育和包膜稳态中可能发挥的作用。这些共同努力将促进我们对生物膜细胞如何相互作用、相互识别和交换细胞物质的机制的理解，从而导致与浮游或分离细胞不同的表型变化。 公共卫生相关性：生物膜是致密的微生物垫，具有重要的医学意义，因为它们是大多数微生物感染的原因。生物膜感染治疗起来困难且昂贵，因为它们对宿主免疫系统和抗菌剂具有抵抗力。该提案旨在研究生物膜中新的细胞相互作用，这可能会增进我们对生物膜的理解，从而改进干预策略。