NASAL COLONIZATION BY S AUREUS--MECHANISMS AND IMMUNITY

金黄色葡萄球菌鼻腔定植——机制和免疫

• 批准号: 6328800
• 负责人: Jean Claire Lee
• 金额: $ 23.16万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6328800
• 关键词: Staphylococcus aureus; Staphylococcus infection; adhesin; age difference; antibacterial antibody; bacteria infection mechanism; bacterial capsules; bacterial vaccines; bactericidal immunity; disease /disorder model; host organism interaction; laboratory mouse; mucosal immunity; protein biosynthesis; surface antigens

Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a diverse spectrum of human and animal diseases. The bacterium may asymptomatically colonize epithelial surfaces, but it also has the invasive potential to cause severe infections, including osteomyelitis, endocarditis, and bacteremia with metastatic complications. The anterior nares serve as a major reservoir of Staphylococcus aureus in humans, and approximately 80 percent of the population are persistent or intermittent carriers. Carriage is a risk factor for S. aureus infection in a number of susceptible populations, including surgical and dialysis patients. Attenuation of carriage with the antibiotic mupirocin has been shown to reduce the prevalence of infection in certain high-risk groups. Since little is known about the host and bacterial factors involved in S. aureus nasal colonization, a mouse model of nasal carriage was developed to study these factors. The overall goal of this study is to utilize this animal model to determine whether the expression of staphylococcal surface antigens influences the establishment of colonization. The mouse nasal colonization model will also be utilized to determine whether mucosal immunization with S. aureus surface antigens can prevent nasal colonization in naive animals. Specific aim 1 is directed at reducing the inoculum needed to establish colonization by utilizing young mice (1 to 4 wks of age) rather than adult mice (6 to 7 wks of age). Under specific aim 2, the role of S. aureus surface antigens in establishing nasal colonization in mice will be assessed. Mutants defective in serotype 5 and 8 capsule expression will be compared with the parental strains for their ability to colonize the nares of mice. Likewise, well-characterized mutants defective in staphylococcal adhesins will be compared with the parental strains for their ability to colonize the nares of mice. Specific aim 3 will determine whether antibodies to S. aureus whole bacteria, capsular polysaccharides, or adhesins will prevent establishment of staphylococcal nasal carriage in mice. Mice will be actively immunized by the subcutaneous or intranasal route or passively immunized intraperitoneally with normal or immune serum antibodies. The results of this study may identify the bacterial factors that promote colonization and reveal potential targets for eliminating S. aureus nasal carriage.

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。细菌可能无疑地将上皮表面定植，但它也具有引起严重感染的侵入性潜力，包括骨髓炎，心内膜炎和菌血症患有转移性并发症。 前鼻孔是人类葡萄球菌金黄色葡萄球菌的主要水库，大约80％的人口是持久或间歇性的载体。 马车是许多敏感人群（包括手术和透析患者）中金黄色葡萄球菌感染的危险因素。 用抗生素mupirocin衰减的衰减已显示可降低某些高危组的感染率。 由于对金黄色葡萄球菌鼻定植的宿主和细菌因子知之甚少，因此开发了一种鼻滚子的小鼠模型来研究这些因素。 这项研究的总体目标是利用该动物模型来确定葡萄球菌表面抗原的表达是否会影响定植的建立。 小鼠鼻殖定模型还将用于确定用金黄色葡萄球菌表面抗原的粘膜免疫是否可以预防天真动物的鼻腔化。特定的目标1用于减少通过利用年轻小鼠（1至4周龄）而不是成年小鼠（6至7周龄）来建立定植所需的接种物。 在特定的目标2下，将评估金黄色葡萄球菌表面抗原在建立小鼠中鼻腔化中的作用。 血清型5和8胶囊表达中有缺陷的突变体将与父母菌株定位小鼠的能力。同样，将葡萄球菌粘附素有缺陷的特征良好的突变体与父母菌株进行比较，因为它们可以定植小鼠的鼻孔。 具体的目标3将确定对金黄色葡萄球菌的全细菌，囊状多糖或粘附素的抗体是否会阻止小鼠葡萄球菌鼻滚子的建立。 小鼠将通过皮下或鼻内途径积极免疫，或用正常或免疫血清抗体被动免疫腹膜内免疫。 这项研究的结果可能会鉴定出促进定殖的细菌因子，并揭示消除金黄色葡萄球菌鼻塞的潜在靶标。