Helper Phage Mobilization of Staphylococcal Enterotoxin Genes

葡萄球菌肠毒素基因的辅助噬菌体动员

• 批准号: 7267947
• 负责人: GAIL E CHRISTIE
• 金额: $ 18.06万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7267947
• 关键词: Address; Affect; Antibiotics; Bacteriophages; Capsid; Communities; DNA Packaging; DNA biosynthesis; Development; Disease; Elements; Enterotoxins; Excision; Family; Frequencies; Genes; Genome; Goals; Head; Human; Infection; Island; Knowledge; Laboratories; Letters; Mediating; Mobile Genetic Elements; Molecular; Morphogenesis; Nosocomial Infections; Numbers; Organism; Pathogenicity Island; Process; Production; Proteins; Public Health; Relative (related person); Research; Resistance; Role; Source; Specific qualifier value; Specificity; Staphylococcus Phages; Staphylococcus aureus; Superantigens; Symptoms; Toxic Shock Syndrome Toxin-1; Toxin; Virion; Virulent; genetic element; hazard; insight; novel; particle; pathogen; prototype; research study; size; staphylococcal enterotoxin; terminase

DESCRIPTION (provided by applicant): Staphylococcus aureus is a dangerous human pathogen responsible for both community acquired disease and nosocomial infections. S. aureus strains cause a variety of disease symptoms due to the production of a wide array of toxins. The emergence of strains resistant to multiple antibiotics, in combination with the horizontal transfer of toxin genes, poses a significant public health hazard. A large number of staphylococcal superantigens, including enterotoxins B, C and toxic shock toxin, have recently been shown to be encoded on a family of related, 15-20 kb pathogenicity islands (SaPIs). The SaPIs represent a novel type of mobile genetic element, which can be transferred at high frequency following helper phage infection. Studies of SaPIs, the prototype element, demonstrated phage-induced excision and replication of the pathogenicity island, followed by the packaging of the pathogenicity island into transducing virions. SaP1 transducing particles resemble those of the helper phage but have heads about 1/3 the volume of the plaque-forming helper phage particles, commensurate with the smaller size of the SaPH genome. SaPH mobilization is highly efficient (about 6 orders of magnitude higher than generalized transduction of chromosomal markers), and thus far has been demonstrated for a single helper phage, 80 alpha. A second superantigen pathogenicity island, SaPI2, is transduced by staphylococcal phage 80 at a frequency similar to that seen for SaPI1 with 80 alpha. The mechanisms underlying the phage-mediated excision, replication and encapsidation of these pathogenicity islands as well as the determinants of the observed phage specificity remain to be elucidated, and represent the long-term goal of this project. The proposed studies will establish the identity and origin of the virion proteins in the smaller SaPI transducing particles. Helper phage and SaPI genes involved in formation of the smaller SaPI capsids will be determined, and the role of a SaPI-encoded small terminase subunit in SaPI DNA packaging will be investigated. These studies will provide insight into the remarkable relationship between two accessory genetic elements that are responsible for the dissemination of staphylococcal enterotoxins. This knowledge will assist in the development of strategies to inhibit the transfer of toxin genes between Staphylococcus aureus strains and help slow the emergence of highly virulent, multiresistant organisms.

描述(申请人提供)：金黄色葡萄球菌是一种危险的人类病原体，可引起社区获得性疾病和医院感染。金黄色葡萄球菌菌株由于产生广泛的毒素而引起各种疾病症状。对多种抗生素产生抗药性的菌株的出现，再加上毒素基因的水平转移，构成了重大的公共卫生危害。最近发现大量的葡萄球菌超抗原，包括肠毒素B、C和毒性休克毒素，编码在一个相关的15-20kb的致病岛(SaPI)家族上。SaPI代表了一种新的可移动的遗传元件，它可以在辅助噬菌体感染后高频转移。对SAPI原型元件的研究表明，噬菌体诱导的致病岛被切除和复制，然后将致病岛包装成转导病毒粒子。SAP1转导颗粒类似于辅助噬菌体的颗粒，但头部约为形成空斑的辅助噬菌体颗粒的三分之一，与较小的SAPH基因组大小相称。SAPH动员的效率很高(比一般的染色体标记转导高出约6个数量级)，到目前为止，已经证明只有一个辅助噬菌体，80α。第二个超抗原致病岛SaPI2由葡萄球菌噬菌体80以与80α的SaPI1相似的频率转导。噬菌体介导的这些致病岛的切除、复制和包裹的潜在机制以及所观察到的噬菌体特异性的决定因素仍有待阐明，并代表了该项目的长期目标。拟议的研究将确定较小的SAPI转导颗粒中的病毒粒子蛋白的身份和来源。将确定参与形成较小SAPI衣壳的辅助噬菌体和SAPI基因，并将研究SAPI编码的小末端酶亚单位在SAPI DNA包装中的作用。这些研究将深入了解导致葡萄球菌肠毒素传播的两个辅助遗传因素之间的显著关系。这一知识将有助于制定战略，以抑制毒素基因在金黄色葡萄球菌菌株之间的转移，并有助于减缓高毒力、多重耐药生物的出现。

项目成果

The phage-related chromosomal islands of Gram-positive bacteria.

• DOI: 10.1038/nrmicro2393
• 发表时间: 2010-08
• 期刊: Nature reviews. Microbiology
• 作者: Novick RP;Christie GE;Penadés JR
• 通讯作者: Penadés JR

A conformational switch involved in maturation of Staphylococcus aureus bacteriophage 80α capsids.

参与金黄色葡萄球菌噬菌体 80α 衣壳成熟的构象转换。

• DOI: 10.1016/j.jmb.2010.11.047
• 发表时间: 2011
• 期刊: Journal of molecular biology
• 影响因子: 5.6
• 作者: Spilman,MichaelS;Dearborn,AltairaD;Chang,JennyR;Damle,PriyadarshanK;Christie,GailE;Dokland,Terje
• 通讯作者: Dokland,Terje