Integrating lipid biosynthesis with bacterial cell cycle progression

将脂质生物合成与细菌细胞周期进程相结合

基本信息

批准号：
8101422
负责人：
Sean Murray
金额：
$ 6.92万
依托单位：
CALIFORNIA STATE UNIVERSITY NORTHRIDGE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8101422
关键词：
Acetates Address Adhesives Advanced Development Affect Alphaproteobacteria Animal Model Antibiotics Bacteria Binding Brucella C-terminal Caulobacter Caulobacter crescentus Cell Cycle Cell Cycle Progression Cell Cycle Proteins Cell Polarity Cell Survival Cell division Cells Cerulenin DNA biosynthesis Data Defect Environment Enzymes Escherichia coli Esters Fatty Acids Fatty acid glycerol esters Flagella Fluorescence Microscopy Gammaproteobacteria Gas Chromatography Genes Genetic Human Link Lipids Location Maps Mastigophora Measures Membrane Membrane Lipids Microbe Molecular Molecular Genetics Monitor Mutation N-terminal Normal Cell Nutrient Phenotype Play Process Protein Overexpression Proteins Public Health Recombinant Proteins Research Proposals Resistance Rickettsia Role Signal Transduction Site Surface Swelling Time Western Blotting antimicrobial fatty acid biosynthesis genetic regulatory protein inhibitor/antagonist interest knockout gene lipid biosynthesis lipid metabolism mutant overexpression pathogenic bacteria prevent promoter protein B public health relevance research study stoichiometry synthetic enzyme vector

项目摘要

DESCRIPTION (provided by applicant): The dimorphic bacterium Caulobacter crescentus is a model organism for studying the bacterial cell cycle. Its asymmetric cell division results in one swarmer and one stalked cell progeny. Motile swarmer cells can not undergo DNA replication until they differentiate into stationary stalked cells. If sufficient nutrients are available, swarmer cells eject their polar flagellum and build a stalk (with adhesive at its end; for attaching to a surface near nutrients) at the same pole formerly occupied by the flagellum. Stalked cells are competent for DNA replication and cell division. During cell division, a flagellum is placed at the pole opposite that of the stalk. Caulobacter's obligate cell cycle is controlled by oscillating master regulators that control different genetic modules in space and time. As a result of this carefully orchestrated process, a flagellum is synthesized only when needed (just prior to cell division) and is placed at the pole opposite that of the stalk. Likewise, a new stalk is synthesized only at the pole previously occupied by a flagellum. This research proposal will address the roles of lipid biosynthesis in this process, using pharmacological, genetic, and molecular approaches. Only by further elucidating the control mechanisms of bacterial cell division can we advance the development of new antimicrobial compounds. Lipid biosynthesisis essential for cell viability and bacterial fatty acid synthetic enzymes have been suggested as antibiotic targets. In fact, compounds specific to bacterial fatty acid biosynthetic compounds have been generated. Most previous studies on bacterial lipid metabolism have focused on E. coli, a gamma-proteobacteria. Caulobacter in contrast, as an alpha-proteobacteria, is closely related to human pathogenic bacteria, such as Brucella and Rickettsia. Thus, the proposed study is relevant to public health. Relevance to Public Health: Fat, also known as lipids or fatty acids play important roles in all cells, from bacteria to humans. Lipids form membranes that separate cells from their environment. This research proposal aims to elucidate the roles of lipids in bacterial cell division. By identifying lipid enzymes important for cell division that are unique to bacteria (i.e. not present in humans), we can identify new antibiotic targets. If we can prevent the synthesis of these lipids, we can prevent bacteria from dividing.

描述（由申请人提供）：二态细菌caulobacter crescentus是用于研究细菌细胞周期的模型生物。它的不对称细胞分裂导致一只蜂群和一个缠扰的细胞后代。在运动堆积细胞分化为固定的茎细胞之前，它们无法进行DNA复制。如果有足够的养分，则在同一极是由鞭毛占据的同一极点，散发出其极性的鞭毛并在其末端粘着茎（以粘合剂的末端；将其连接到养分附近的表面上）。茎细胞具有DNA复制和细胞分裂的能力。在细胞分裂期间，将鞭毛放在茎相对的极点。 Caulobacter的强制性细胞周期是通过控制空间和时间上不同遗传模块的主调节器来控制的。由于这一精心策划的过程，仅在需要时（就在细胞分裂之前）合成鞭毛，并将其放在茎相对的极点。同样，只有在先前由鞭毛占据的杆上合成一个新的茎。该研究建议将使用药理学，遗传和分子方法来解决此过程中脂质生物合成的作用。只有通过进一步阐明细菌细胞分裂的控制机制，我们才能推进新的抗菌化合物的发展。脂质生物合成对于细胞活力和细菌脂肪酸合成酶必不可少的必不可少，已被认为是抗生素靶标。实际上，已经产生了针对细菌脂肪酸生物合成化合物的化合物。先前关于细菌脂质代谢的大多数研究都集中在大肠杆菌（Gamma-甲状腺细菌）大肠杆菌上。相比之下，花椰菜作为α-蛋白细菌，与人类的致病细菌（如布鲁氏菌和立克西亚）密切相关。因此，拟议的研究与公共卫生有关。与公共卫生相关：脂肪，也称为脂质或脂肪酸在从细菌到人类的所有细胞中都起着重要作用。脂质形成膜，将细胞与环境区分开。该研究建议旨在阐明脂质在细菌细胞分裂中的作用。通过鉴定对细菌独有的细胞分裂脂质酶（即在人类中不存在），我们可以鉴定出新的抗生素靶标。如果我们可以防止这些脂质的合成，则可以防止细菌分裂。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adaption of Synechococcus sp. IU 625 to growth in the presence of mercuric chloride.

聚球藻属的适应。

DOI：
10.1016/j.acthis.2011.01.004
发表时间：
2012
期刊：
Acta histochemica
影响因子：
2.5
作者：
Chu,Tin-Chun;Murray,SeanR;Todd,Jennifer;Perez,Winder;Yarborough,JonathanR;Okafor,Chiedozie;Lee,LeeH
通讯作者：
Lee,LeeH

Use of bacteria for rapid, pH-neutral, hydrolysis of the model hydrophobic carboxylic acid ester p-nitrophenyl picolinate.

使用细菌快速、pH 中性水解模型疏水性羧酸酯对硝基苯基吡啶甲酸。

DOI：
10.3109/10242422.2012.702269
发表时间：
2012
期刊：
Biocatalysis and biotransformation
影响因子：
1.8
作者：
Forest,AlexandraE;Goldstine,GordonG;Schrodi,Yann;Murray,SeanR
通讯作者：
Murray,SeanR

Physiological effects of nickel chloride on the freshwater cyanobacterium Synechococcus sp. IU 625.

DOI：
10.4236/abb.2013.47a2002
发表时间：
2013-07
期刊：
Advances in bioscience and biotechnology (Print)
影响因子：
0
作者：
Nohomovich B;Nguyen BT;Quintanilla M;Lee LH;Murray SR;Chu TC
通讯作者：
Chu TC

The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication.

新月柄杆菌 ctrA P1 启动子对于协调细胞周期事件至关重要，防止 DNA 复制过度启动。

DOI：
10.1099/mic.0.055285-0
发表时间：
2012
期刊：
Microbiology (Reading, England)
影响因子：
0
作者：
Schredl,AlexanderT;PerezMora,YannetG;Herrera,Anabel;Cuajungco,MathP;Murray,SeanR
通讯作者：
Murray,SeanR

Temperature-induced activation of freshwater Cyanophage AS-1 prophage.