Transcriptional Regulation of a major virulence operon in Staphylococcus aureus: Insights from biochemcial genomic and proteomic studies

金黄色葡萄球菌主要毒力操纵子的转录调控：生化基因组和蛋白质组学研究的见解

• 批准号: BB/I001492/1
• 负责人: Sivaramesh Wigneshweraraj
• 金额: $ 42.34万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI001492%2F1
• 关键词: Transcriptional; Regulation; major; virulence; operon

Staphylococcus aureus is a bacterium that is often referred to as a 'superbug' because of its ability to cause a diverse range of human and animal diseases and to resist antibiotic treatment (e.g. the MRSA-strain). S. aureus is a major human and animal pathogen because it can produce a wide range of virulence factors, which allow the bacterium to attach itself to the host, evade the host immune system and to rapidly degrade host tissue through the production of potent toxins, e.g. haemolysins which break down blood cells. The expression of genes in S. aureus responsible for the production of virulence factors are tightly controlled by several gene regulatory systems. It is generally accepted that the so called 'agr system' is the 'master' regulatory system involved in the control and expression of virulence genes in S. aureus. Here, we propose to study how the expression of the 'agr system' itself is controlled in the different stages of growth of S. aureus cells and in response to the environmental conditions encountered by S. aureus cells during growth and infection. In particular, we will describe and indentify the component interactions between proteins and DNA that contribute to 'switching on' the agr system. This study will provide one of the fewest examples, where a major virulence-linked gene regulatory system is described at the molecular level in a clinically significant bacterial pathogen. Thus, the outcome of this research will generate valuable resources and a knowledge base for the academic and clinical research communities and those in industrial settings seeking to exploit the agr system to create novel drugs for the treatment of staphylococcal infections.

金黄色葡萄球菌是一种通常被称为“超级细菌”的细菌，因为它能够引起多种人类和动物疾病并抵抗抗生素治疗（例如MRSA菌株）。S.金黄色葡萄球菌是主要的人类和动物病原体，因为它可以产生广泛的毒力因子，这些毒力因子允许细菌将其自身附着到宿主上，逃避宿主免疫系统，并通过产生强效毒素（例如分解血细胞的溶血素）来快速降解宿主组织。基因在S.负责产生毒力因子的金黄色葡萄球菌受到几种基因调控系统的严格控制。人们普遍认为，所谓的“agr系统”是参与S毒力基因控制和表达的“主”调节系统。金黄色。在这里，我们建议研究如何表达的“agr系统”本身是控制在不同阶段的增长S。金黄色葡萄球菌细胞和响应于S.金黄色葡萄球菌细胞生长和感染过程中。特别是，我们将描述和识别有助于“打开”agr系统的蛋白质和DNA之间的组件相互作用。这项研究将提供一个最少的例子，其中一个主要的毒力连锁基因调控系统是在分子水平上描述了一个临床上显着的细菌病原体。因此，这项研究的结果将为学术和临床研究团体以及那些寻求利用agr系统来创造治疗葡萄球菌感染的新药的工业环境中的人产生有价值的资源和知识基础。

项目成果

Naturally occurring polymorphisms in the virulence regulator Rsp modulate Staphylococcus aureus survival in blood and antibiotic susceptibility.

• DOI: 10.1099/mic.0.000695
• 发表时间: 2018-09
• 期刊: Microbiology (Reading, England)
• 作者: Krishna A;Holden MTG;Peacock SJ;Edwards AM;Wigneshweraraj S
• 通讯作者: Wigneshweraraj S

Transcriptional downregulation of agr expression in Staphylococcus aureus during growth in human serum can be overcome by constitutively active mutant forms of the sensor kinase AgrC.

• DOI: 10.1111/1574-6968.12309
• 发表时间: 2013-12
• 期刊: FEMS microbiology letters
• 影响因子: 2.1
• 作者: James EH;Edwards AM;Wigneshweraraj S
• 通讯作者: Wigneshweraraj S

Systematic mutational analysis of the LytTR DNA binding domain of Staphylococcus aureus virulence gene transcription factor AgrA.

• DOI: 10.1093/nar/gku1015
• 发表时间: 2014-11-10
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Nicod SS;Weinzierl RO;Burchell L;Escalera-Maurer A;James EH;Wigneshweraraj S
• 通讯作者: Wigneshweraraj S