B SUBTILIS ECF SIGMA FACTORS: ROLES AND REGULATION
枯草芽孢杆菌 ECF 西格玛因素:作用和监管
基本信息
- 批准号:6490048
- 负责人:
- 金额:$ 27.83万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-05-01 至 2004-12-31
- 项目状态:已结题
- 来源:
- 关键词:Bacillus subtilis DNA directed RNA polymerase antibiotics bacterial genetics bacterial proteins cell wall drug resistance enzyme activity enzyme mechanism gene expression genetic regulatory element nucleic acid sequence protein structure function proteomics site directed mutagenesis transcription factor
项目摘要
DESCRIPTION (adapted from the investigator's summary): The widespread emergence
of antibiotic resistant bacteria poses a grave threat to our ability to manage
and control infectious disease. While tremendous progress has been made in
understanding the role of transmissible plasmids and high-level resistance
genes in antibiotic resistance, the role and regulation of
chromosomally-encoded determinants is less well understood. This project
focuses on the genetically well characterized model organism Bacillus subtilis,
to investigate the functional genomics of antibiotic resistance and responses.
The close evolutionary between B. subtilis and important human pathogens
(especially Staphylococcus aureus, Mycobacterium tuberculosis, Enterococcus,
and Streptococcus), allows knowledge gained in our system to be directly used
in understanding the other.
The goal of this project is to understand the role of alternative sigma factors
in coordinating the genetic responses triggered by exposure of B. subtilis to
antibiotics that target the cell envelope. Recently, the SigX and SigW
regulators have been found to activate transcription of a large number of genes
affecting the structure and function of cell surface polymers, antibiotic
resistance mechanisms, and the production of antimicrobial peptides. Expression
of these sigma factors is strongly induced by several clinically important
antibiotics, including vancomycin and cephalospirins.
To better define these genetic responses, and their roles in protecting the
cell against antibiotics, two aims will be pursued. First, promoters controlled
by each sigma factor will be identified and the rules that govern promoter
selectivity will be explored. The identification of target promoters will
reveal the complete set of genes (the regulon) activated by each sigma. The PI
will define the overlap the overlap between the various regulons controlled by
SigX, SigW and other sigma factors. This aim will include both proteomics and
genomics based approaches. Second, the physiological roles of selected taarget
genes will also be investigated. For this aim the PI will focus on those
operons implicated on defense against antibiotics, modification of the cell
envelope, or the production of antimicrobial compounds. In addition, the
signaling pathways that control the expression of these regulons will be
investigated. Although many different antibiotics can induce each regulon, it
is likely that these antibiotics lead to the accumulation of common signaling
molecules that are perceived by the anti-sigma factor which then releases the
sigma factor. Genetic approaches have been devised to identify components of
these signaling pathways. Together, these two aims will provide a unified
picture of these two large regulons and their roles in B. subtilis physiology.
描述(改编自研究者总结):
抗生素耐药细菌的数量对我们管理
控制传染病。虽然在这方面取得了巨大进展,
了解可传播质粒和高水平耐药性的作用
基因在抗生素耐药性中的作用和调控
染色体编码的决定簇还不太清楚。这个项目
集中于遗传上良好表征的模式生物枯草芽孢杆菌,
研究抗生素耐药性和反应的功能基因组学。
B.枯草杆菌和重要的人类病原体
(尤其是金黄色葡萄球菌,结核分枝杆菌,肠球菌,
和链球菌),允许直接使用我们系统中获得的知识
了解对方。
这个项目的目标是了解替代西格玛因素的作用
协调由接触B引发的遗传反应。枯草到
针对细胞被膜的抗生素最近,SigX和SigW
已经发现调节子激活大量基因的转录
影响细胞表面聚合物的结构和功能,
耐药机制和抗菌肽的生产。表达
这些sigma因素的强烈诱导的几个临床重要的
抗生素,包括万古霉素和头孢菌素。
为了更好地定义这些遗传反应,以及它们在保护
细胞对抗抗生素,将追求两个目标。首先,发起人控制
每个西格玛因素将被确定,
将探索选择性。目标启动子的鉴定将
揭示了由每个sigma激活的完整的基因组(调节子)。的PI
将定义各种调节子之间的重叠
SigX、SigW和其他sigma因子。这一目标将包括蛋白质组学和
基于基因组学的方法第二,所选目标的生理作用
基因也将被研究。为此,PI将重点关注
操纵子涉及对抗生素的防御,细胞的修饰
包膜或抗菌化合物的生产。此外该
控制这些调节子表达的信号通路将被
研究了虽然许多不同的抗生素可以诱导每个调节子,
这些抗生素很可能会导致共同信号的积累,
反西格玛因子感知到的分子,
西格玛因子遗传学方法已经被设计来鉴定
这些信号通路。这两个目标将共同提供一个统一的
这两个大的调节子和它们在B中的作用。枯草生理学
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John D Helmann其他文献
The σ70family of sigma factors
- DOI:
10.1186/gb-2003-4-1-203 - 发表时间:
2003-01-01 - 期刊:
- 影响因子:9.400
- 作者:
Mark SB Paget;John D Helmann - 通讯作者:
John D Helmann
John D Helmann的其他文献
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{{ truncateString('John D Helmann', 18)}}的其他基金
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