Impact of the Nasal Microbiome on S. aureus Colonization and Infection

鼻腔微生物组对金黄色葡萄球菌定植和感染的影响

• 批准号: 8696834
• 负责人: MARY BESSESEN
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8696834
• 关键词: Admission activity; Anterior nares; Anti-Bacterial Agents; Bacteremia; Bacteria; Baseline Surveys; Case-Control Studies; Clinical; Coagulase; Code; Community-Acquired Infections; Complex; Corynebacterium; Cross-Sectional Studies; DNA Sequence; Data; Development; Diagnosis; Disease; Environment; Event; Frequencies; Functional disorder; Genus staphylococcus; Goals; Health; Hospitals; Host Defense; Human; Incidence; Individual; Infection; Infection Control; Infection prevention; Inpatients; Laboratories; Lead; Link; Lung; Metagenomics; Methicillin; Methicillin Resistance; Modality; Morbidity - disease rate; Nasal cavity; Nature; Nose; Operative Surgical Procedures; Organism; Patients; Persons; Population; Prevention; Probiotics; Propionibacterium acnes; Pulsed-Field Gel Electrophoresis; Relative (related person); Ribosomal RNA; Risk; Risk Factors; Role; Sampling; Sepsis; Site; Skin Tissue; Source; Specimen; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus pneumoniae; Technology; Time; Variant; Veterans; attributable mortality; bacteriocin; base; case control; cohort; commensal microbes; high risk; improved; innovation; methicillin resistant Staphylococcus aureus; microbial; microbial community; microbiome; microorganism; mortality; novel; pathogen; prevent; programs; resistant strain; screening; small molecule; soft tissue; transmission process

DESCRIPTION (provided by applicant): Staphylococcus aureus infections of the bloodstream, lung, surgical sites, and skin and soft tissues are a leading cause of morbidity and mortality. The attributable mortality associated with methicillin sensitive S. aureus bloodstream infection is 19% and this rises to 33% if S. aureus is methicillin resistant(MRSA). More than 50% of S. aureus clinical isolates at DVAMC-Denver are methicillin-resistant, and MRSA is endemic in many VA hospitals nationwide, leading to national efforts to control the problem. Nasal colonization with S. aureus is a source of transmission to other persons, and a major risk factor for subsequent infection in colonized individuals. For example, patients who are colonized at the time of hospital admission have a three-fold higher risk of bloodstream infection with S. aureus, and preliminary data from DVAMC-Denver indicate that MRSA colonization is associated with an 8-fold increased risk for MRSA bacteremia. Decolonization therapy reduces the risk of infection, supporting the hypothesis that colonization leads to infection. We hypothesize that nasal commensal microbes (the nasal microbiome) may inhibit or promote S. aureus nasal colonization. Results from a cross-sectional study of hospital inpatients support this hypothesis. Previous studies of microorganisms competing with S. aureus for the anterior nares niche have focused on individual species, e.g. Staphylococcus epidermidis, Streptococcus pneumoniae, Corynebacterium spp., isolated from culture. There is a growing body of evidence that microorganisms exist in nature as consortia, and that study of them in this fashion may advance our understanding of their competitive environment. The microbial consortia that normally inhabit the nasal cavity may be difficult to culture on routine media, so its impact on S. aureus colonization remains poorly characterized. To identify microbial species associated with a lower risk of MRSA colonization, we propose to prospectively characterize the human nares microbiota in a well-defined cohort of subjects. A program of active screening of hospital inpatients for nasal MRSA colonization is part of the VHA national effort to control MRSA in hospitalized veterans, and provides an opportunity to gather samples in a longitudinal fashion, clearly define persons as non-carriers, persistent carriers or intermittent carriers, and identify differences between these groups in nasal microbiota. We will comprehensively determine the nares microbiota in specimens collected longitudinally, using innovative DNA sequence-based technologies (16S rRNA metagenomics) and correlate these data with MRSA colonization and infection. Our understanding of the complex interactions among populations of bacteria is only beginning, and may lead to new strategies that can be harnessed to improve human health. Possibilities include development of probiotic therapies, identification of bacteriocins produced by MRSA-inhibitory commensals, which may be applied to the nares or other body sites to prevent colonization, and synthesis of small molecule congeners of bacteriocins that may be useful as systemic antibacterial agents.

描述（由申请人提供）： 血液、肺部、手术部位以及皮肤和软组织的金黄色葡萄球菌感染是发病和死亡的主要原因。与甲氧西林敏感的金黄色葡萄球菌血流感染相关的归因死亡率为 19%，如果金黄色葡萄球菌具有甲氧西林耐药性 (MRSA)，则该死亡率将上升至 33%。 DVAMC-Denver 超过 50% 的金黄色葡萄球菌临床分离株对甲氧西林具有耐药性，并且 MRSA 在全国许多 VA 医院中流行，导致全国努力控制这一问题。 金黄色葡萄球菌的鼻定植是传播给其他人的来源，也是定植个体随后感染的主要危险因素。例如，入院时被定植的患者发生金黄色葡萄球菌血流感染的风险增加三倍，DVAMC-丹佛的初步数据表明，MRSA 定植与 MRSA 风险增加 8 倍相关菌血症。去定植治疗可降低感染风险，支持定植导致感染的假设。 我们假设鼻共生微生物（鼻微生物组）可能抑制或促进金黄色葡萄球菌鼻定植。对医院住院患者进行的横断面研究的结果支持了这一假设。先前关于微生物与金黄色葡萄球菌竞争前鼻孔生态位的研究主要集中在单个物种上，例如金黄色葡萄球菌。从培养物中分离出表皮葡萄球菌、肺炎链球菌、棒状杆菌属。越来越多的证据表明，微生物在自然界中以联合体的形式存在，以这种方式对它们进行研究可能会增进我们对其竞争环境的理解。通常栖息于鼻腔的微生物群落可能难以在常规培养基上培养，因此其对金黄色葡萄球菌定植的影响仍不清楚。为了确定与 MRSA 定植风险较低相关的微生物种类，我们建议前瞻性地描述一组明确的受试者中的人类鼻孔微生物群。对医院住院患者鼻部 MRSA 定植进行主动筛查的计划是 VHA 控制住院退伍军人 MRSA 的国家努力的一部分，并提供了纵向收集样本的机会，明确将人员定义为非携带者、持续携带者或间歇性携带者携带者，并确定这些群体之间鼻腔微生物群的差异。我们将使用基于 DNA 序列的创新技术（16S rRNA 宏基因组学）全面确定纵向收集的标本中的鼻孔微生物群，并将这些数据与 MRSA 定植和感染相关联。我们对细菌群体之间复杂相互作用的理解才刚刚开始，可能会带来可用于改善人类健康的新策略。可能性包括开发益生菌疗法、鉴定由 MRSA 抑制性共生菌产生的细菌素（可应用于鼻孔或其他身体部位以防止定植），以及合成可用作全身抗菌剂的细菌素小分子同系物。