Biological relevance of capsule expression by S. aureus

金黄色葡萄球菌荚膜表达的生物学相关性

• 批准号: 6863705
• 负责人: Jean Claire Lee
• 金额: $ 3.2万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6863705
• 关键词: Staphylococcus aureus; bacteria infection mechanism; bacterial capsules; bacterial genetics; bacterial polysaccharides; enzyme mechanism; fibrinogen; gene expression; gene targeting; genetically modified animals; kidney disorder; laboratory mouse; mammary disorder; polymerase chain reaction; septicemia; southern blotting; virulence

DESCRIPTION (provided by applicant) Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a diverse spectrum of human and animal diseases. Approximately 75% of S. aureus strains from humans are encapsulated. The prevalence of encapsulation among bovine isolates is variable, depending upon the geographic source of the isolate. An understanding of the role of the staphylococcal capsule in the pathogenesis of S. aureus infections is important. This FIRCA application is a supplement to Dr. Jean Lee's RO1 AI29040 grant to study the genetics of capsule production by S. aureus. The proposed research will be performed primarily in Argentina at the University of Buenos Aires by Dr. Daniel Sordelli and his colleagues. The objectives of the FIRCA project complement those of Dr. Lee's grant and are specifically related to specific aim #3. Under that aim, S. aureus isolates have been identified that lack the capsule genetic locus and carry an IS257-1ike element in its place. The proposed study will: 1) Investigate the loss of the cap5/8 gene cluster in NT S. aureus and the potential role of the IS257 element in such a mechanism. Whether copies of IS257 are associated with cap5/8 locus in S. aureus and whether loss of the cap5(8) genes can occur in vivo will be determined. The in vivo infections will include a systemic model of bacteremia leading to renal abscess formation and the mouse mastitis model of localized infection. 2) Determine whether CP5 or CP8 production enhances staphylococcal virulence in a mouse model of experimental mastitis. 3) Evaluate the effect of CP expression on S. aureus clumping factor A-mediated adherence to fibrinogen. The proposed research will permit further exploration of issues not covered by our currently funded projects, and the information that will emerge from it will expand our knowledge of S. aureus capsular polysaccharide biology.

描述（由申请人提供） 金黄色葡萄球菌是负责各种人类和动物疾病的机会性细菌病原体。大约75％的金黄色葡萄球菌菌株封装。牛分离株之间封装的普遍性是可变的，这取决于分离株的地理来源。了解葡萄球菌囊在金黄色葡萄球菌感染发病机理中的作用很重要。该FIRCA应用是对Jean Lee博士的RO1 AI29040赠款的补充，用于研究S. Aureus的胶囊生产遗传学。拟议的研究将主要由丹尼尔·索德利（Daniel Sordelli）博士及其同事在布宜诺斯艾利斯大学的阿根廷进行。 FIRCA项目的目标补充了李博士的赠款，并特别与特定目标＃3有关。在该目标下，已经确定了金黄色葡萄球菌分离株缺乏胶囊遗传基因座并携带IS257-1的元素。拟议的研究将：1）研究NT金黄色葡萄球菌中CAP5/8基因簇的损失，以及IS257元素在这种机制中的潜在作用。 IS257的副本是否与金黄色葡萄球菌中的CAP5/8基因座有关，并且将确定在体内丢失CAP5（8）基因的丢失。体内感染将包括菌血症的系统性模型，导致肾脓肿形成和局部感染的小鼠乳腺炎模型。 2）确定CP5或CP8的产生是否会增强实验性乳腺炎小鼠模型中的葡萄球菌毒力。 3）评估CP表达对金黄色葡萄球菌块状因子A介导的粘附于纤维蛋白原的影响。拟议的研究将允许进一​​步探索我们当前资助的项目未涵盖的问题，从中出现的信息将扩大我们对金黄色葡萄球菌囊囊多糖生物学的了解。