Sinorhizobium meliloti factors that affect biofilm formation and symbiosis efficiency

影响生物膜形成和共生效率的苜蓿中华根瘤菌因子

基本信息

批准号：
10672247
负责人：
Joseph Chiung-Chu Chen
金额：
$ 11.63万
依托单位：
SAN FRANCISCO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10672247
关键词：
Adherence Adhesions Affect Alphaproteobacteria Antibiotic Resistance Antimicrobial Resistance Bacteria Bacterial Adhesins Brucella Carbon Cell Aggregation Cell Polarity Cell model Cell physiology Cells Chemicals Citrus Desiccation Development Disadvantaged Disease Elements Environment Environmental Risk Factor Expression Profiling Fabaceae Funding Genes Genetic Genetic Models Genetic Transcription Goals GpGp Gram-Negative Bacteria Grant Health Heterogeneity Homeostasis Horizontal Gene Transfer Human Immune response Industrialization Infection Invaded Investigation Laboratories Length Link Medical Device Microbe Microbial Biofilms Modeling Molecular Monitor Mutagenesis Mutation Nitrogen Nodule Nonsense Mutation Nutrient Organism Pathogenesis Pathway interactions Periodicity Phenotype Physiological Plants Play Poison Polymers Preparation Prevention Process Production Productivity Property Public Health Regulation Research Research Personnel Research Training Role Scientific Advances and Accomplishments Second Messenger Systems Signal Transduction Sinorhizobium meliloti Stress Students Surface Symbiosis System Tissues antimicrobial drug career cell community cell motility chronic infection diguanylate cyclase experience host colonization host-microbe interactions human pathogen improved insight medical implant microbial microbial disease microorganism mutant mutation correction pathogen phosphoric diester hydrolase prevent protein function recurrent infection symbiont transcription factor

项目摘要

Project Summary / Abstract The proposed project will elucidate the mechanisms that control polar adhesin production, biofilm formation, and host colonization in alpha-proteobacteria, a physiologically heterogeneous group that includes a number of significant human pathogens. Particularly relevant to public health, biofilm formation plays a crucial role in the survival of bacteria in diverse environments: cells in biofilms attach recalcitrantly to biotic and abiotic surfaces, develop increased resistance to antimicrobial agents, and contribute to persistent infections. Although limiting biofilm formation has the potential to prevent and restrict microbial diseases, little is known about biofilm formation by alpha-proteobacteria and how it facilitates host colonization. We previously discovered a biofilm-associated mutation common in laboratory strains of Sinorhizobium meliloti, a model alpha-proteobacterium that forms mutualistic symbiosis with compatible legumes by colonizing root tissues and fixing nitrogen in exchange for nutrients from plant hosts. Correcting the mutation restored full-length production of the conserved polarity factor PodJ, thus enabling synthesis of the holdfast (a polar adhesin) and assembly of robust biofilms, phenotypes never observed before. We found that biofilm- competent strains possess a competitive advantage over biofilm-deficient strains during host infection. Via transposon mutagenesis, we identified a number of genes involved in biofilm development, including one encoding a conserved transcription factor (LdtR) and another encoding a diguanylate cyclase and phosphodiesterase, known to modulate levels of the c-di-GMP second messenger. The goals of this proposal are (a) to decipher the responsibilities of key regulators during biofilm formation and host colonization and (b) to establish a system for monitoring the relationship between symbiosis and environmental factors. We plan to achieve these goals by accomplishing the following three specific aims. (1) We will determine how LdtR expression is regulated and what cellular functions it performs. (2) We will assess how factors that modulate c- di-GMP levels contribute to biofilm formation and host infection. (3) We will evaluate whether symbiosis affects host response to toxic compounds and how chemical stress and other microbes influence host-symbiont interactions. Results from the investigation will provide a better model of how cellular and external factors can contribute to adhesion, biofilm formation, and host invasion in alpha-proteobacteria. In addition to accomplishing the scientific objectives described above, funding of this proposal will enhance the research productivity and grant competitiveness of the investigator and allow students, particularly those from underrepresented backgrounds, to gain research training and preparation for biomedical careers.

项目摘要 /摘要拟议的项目将阐明控制极性粘附素，生物膜的机制形成和宿主在α-蛋白杆菌中的殖民化，这是一种生理异质组，包括一个大量人类病原体的数量。与公共卫生特别相关，生物膜形成起着至关重要的作用在各种环境中细菌存活中的作用：生物膜中的细胞顽固地附着于生物和非生物上表面，增强对抗菌剂的耐药性，并导致持续感染。尽管限制生物膜的形成有可能预防和限制微生物疾病，但知之甚少关于α-甲状腺细菌及其如何促进宿主定殖的生物膜形成。我们以前发现了在Sinorhizobium实验室菌株中常见的生物膜相关突变 Meliloti，一种模型α-杆菌，形成互生共生，由兼容豆类。定居根组织并固定氮，以换取植物宿主的养分。纠正突变恢复了保守极性因子PODJ的全长产生，因此可以合成Holdfast（A 极性生物膜的极性粘合剂和组装，表型从未观察到。我们发现生物膜 - 在宿主感染期间，有能力的菌株比生物膜缺陷菌株具有竞争优势。通过转座子诱变，我们确定了许多参与生物膜发育的基因，包括一个编码保守的转录因子（LDTR）和另一个编码二烷基酸酯环化酶和磷酸二酯酶，已知可以调节C-DI-GMP第二信使的水平。该提议的目标是（a）在生物膜形成和宿主定殖过程中破译关键调节剂的责任和（b）建立一个系统来监视共生与环境因素之间的关系。我们计划通过实现以下三个特定目标来实现这些目标。（1）我们将确定LDTR如何表达受调节及其执行的细胞功能。（2）我们将评估调节c-的因素如何 DI-GMP水平有助于生物膜形成和宿主感染。（3）我们将评估共生是否影响宿主对有毒化合物的反应以及化学胁迫和其他微生物如何影响宿主 - 共生体互动。调查的结果将为细胞和外部因素如何可以提供更好的模型有助于α-细菌中的粘附，生物膜形成和宿主侵袭。除了实现上述科学目标外，该提议的资金还将提高研究生产力并授予研究人员的竞争力，并允许学生，特别是那些来自代表性不足的背景的人，以获得生物医学职业的研究培训和准备。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Optical disassembly of cellular clusters by tunable 'tug-of-war' tweezers.

DOI：
10.1038/lsa.2016.158
发表时间：
2016
期刊：
Light, science & applications
影响因子：
0
作者：
通讯作者：

Jungle Express is a versatile repressor system for tight transcriptional control.

DOI：
10.1038/s41467-018-05857-3
发表时间：
2018-09-06
期刊：
Nature communications
影响因子：
16.6
作者：
Ruegg TL;Pereira JH;Chen JC;DeGiovanni A;Novichkov P;Mutalik VK;Tomaleri GP;Singer SW;Hillson NJ;Simmons BA;Adams PD;Thelen MP
通讯作者：
Thelen MP

Evaluating the toxic effect of an antimicrobial agent on single bacterial cells with optical tweezers.