Epidemic CA-MRSA: Molecular Epidemiology and Immunology

流行性 CA-MRSA：分子流行病学和免疫学

• 批准号: 8457141
• 负责人: Maria-Luisa Alegre
• 金额: $ 32.01万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8457141
• 关键词: Accident and Emergency department; Address; Adult; Am 80; Ancillary Study; Antibiotic Therapy; Antibiotic susceptibility; Area; Attention; Award; B-Lymphocytes; Bacteria; Bacterial Infections; Biology; Blood Cells; Budgets; California; Caring; Cells; Centers for Disease Control and Prevention (U.S.); Chicago; Child; Clindamycin; Clinical Treatment; Communicable Diseases; Communities; Contracts; Data; Defect; Detection; Development; Disease; Double-Blind Method; Emergency Care; Enrollment; Environment; Epidemic; Evaluation; Exposure to; Frequencies; Funding; General Population; Genetic; Goals; Healthcare; Immune; Immune response; Immune system; Immunologics; Immunologist; Incidence; Individual; Infection; Infectious Skin Diseases; Integration Host Factors; Interleukin-17; Investigation; Libraries; Light; Los Angeles; Measures; Mediating; Medical; Molecular; Molecular Epidemiology; Molecular Immunology; Monobactams; National Institute of Allergy and Infectious Disease; Normal Statistical Distribution; Pathogenicity; Patients; Placebos; Plasma; Play; Population; Predisposition; Prevention; Prevention strategy; Production; Property; Public Health; Randomized; Research; Research Personnel; Role; San Francisco; Schedule; Skin Tissue; Soft Tissue Infections; Staphylococcus aureus; T-Lymphocyte; Testing; Trimethoprim; Trimethoprim-Sulfamethoxazole; Universities; Vaccines; Virulent; combat; cytokine; disorder prevention; extracellular; fighting; insight; methicillin resistant Staphylococcus aureus; microbial; multidisciplinary; novel therapeutics; prevent; prospective; public health relevance; randomized trial; research study; response; treatment strategy

DESCRIPTION (provided by applicant): We are proposing studies utilizing the patients enrolled in the DMID-funded "Randomized, Double-Blind Trial of Clindamycin, Trimethoprim-Sulfamethoxazole, or Placebo for Uncomplicated Skin and Soft Tissue Infections Caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA)." This contract by NIAID to the Co-PI at the University of Chicago as well as investigators at the University of California/San Francisco, Harbor-University of California/Los Angeles, has provided a unique opportunity to explore unaddressed issues. About 375 children and adults with skin and soft tissue infections (SIs) will be enrolled for a period of three years at the University of Chicago. Preliminary data indicate that about 84% of enrollees will have a S. aureus SI, providing a unique opportunity to perform additional research addressing the underlying cause for increased susceptibility to SIs in the general population. In the last decade the incidence and frequency of MRSA infections has increased exponentially, particularly among otherwise healthy individuals, to the extent that CA-MRSA has become epidemic in the US and is now a public health imperative. The recognition that CA-MRSA strains can both spread rapidly and cause severe disease mandates a need for urgent investigation to understand the molecular microbial pathogenicity and underlying host immune responses. Accordingly, we have assembled a multidisciplinary team of microbiologists, infectious disease experts, and immunologists to explore simultaneously several areas likely to yield important insights into the biology of the CA-MRSA epidemic, with a focus on the role of host immune responses in CA-MRSA infection. Studies detailed in this proposal will provide substantial insight into the contributions of host innate and adaptive mechanisms to infection susceptibility. It is hoped that new information will guide novel therapeutic and preventive strategies to combat CA-MRSA infection.

描述（由申请人提供）：我们建议使用DMID资助的“克林霉素、甲氧苄啶-磺胺甲恶唑或安慰剂治疗社区相关耐甲氧西林金黄色葡萄球菌（CA-MRSA）引起的无并发症皮肤和软组织感染的随机、双盲试验”中招募的患者进行研究。“NIAID与芝加哥大学的Co-PI以及加州大学/弗朗西斯科分校、加州大学/洛杉矶分校的调查人员签订的这份合同，为探索未解决的问题提供了一个独特的机会。大约375名患有皮肤和软组织感染（SI）的儿童和成人将在芝加哥大学接受为期三年的研究。初步数据表明，大约84%的注册者将有一个S。金黄色葡萄球菌SI，提供了一个独特的机会，进行额外的研究，解决的根本原因增加敏感性的SI在一般人群。在过去的十年中，MRSA感染的发病率和频率呈指数级增加，特别是在其他健康个体中，CA-MRSA在美国已经成为流行病，现在是公共卫生的当务之急。认识到CA-MRSA菌株可以迅速传播并引起严重疾病，需要进行紧急调查，以了解分子微生物致病性和潜在的宿主免疫反应。因此，我们组建了一个由微生物学家、传染病专家和免疫学家组成的多学科团队，同时探索可能对CA-MRSA流行病生物学产生重要见解的几个领域，重点关注宿主免疫反应在CA-MRSA感染中的作用。本提案中详细介绍的研究将为宿主先天和适应机制对感染易感性的贡献提供实质性的见解。希望新的信息将指导新的治疗和预防策略，以打击CA-MRSA感染。

项目成果

Retrospective Identification of a Broad IgG Repertoire Differentiating Patients With S. aureus Skin and Soft Tissue Infections From Controls.

回顾性鉴定广泛的 IgG 谱系，以区分金黄色葡萄球菌皮肤和软组织感染患者与对照组。

• DOI: 10.3389/fimmu.2019.00114
• 发表时间: 2019
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Rigat,Fabio;Bartolini,Erika;Dalsass,Mattia;Kumar,Neha;Marchi,Sara;Speziale,Pietro;Maione,Domenico;Chen,Luqiu;Romano,MariaRosaria;Alegre,Maria-Luisa;Bagnoli,Fabio;Daum,RobertS;David,MichaelZ
• 通讯作者: David,MichaelZ