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，外科部位以及皮肤和软组织的金黄色葡萄球菌感染是发病率和死亡率的主要原因。与甲氧西林敏感的金黄色葡萄球菌感染相关的可归因死亡率为19％，如果金黄色葡萄球菌具有甲氧西林耐药性（MRSA），则该死亡率上升至33％。 DVAMC-Denver的金黄色葡萄球菌临床分离株中有50％以上是耐甲氧西林的，MRSA在全国许多VA医院中都是地方性的，导致了国家控制该问题的国家努力。 金黄色葡萄球菌的鼻定植是向其他人传播的来源，也是殖民个体随后感染的主要风险因素。例如，在入院时被殖民的患者患有金黄色葡萄球菌感染血液的风险增加了三倍，而来自DVAMC-denver的初步数据表明，MRSA定殖与MRSA细菌的增加8倍有关。非殖民化疗法降低了感染的风险，支持定殖导致感染的假设。 我们假设鼻腔共生微生物（鼻腔微生物组）可能抑制或促进金黄色葡萄球菌鼻腔化。医院住院患者的横断面研究的结果支持了这一假设。先前对与金黄色葡萄球菌为前奈斯壁ni族竞争的微生物的研究重点是单个物种，例如葡萄球菌表皮，肺炎链球菌，corynebacterium spp。，从培养物中分离出来。越来越多的证据表明，自然界存在微生物作为财团，并且以这种方式进行研究可能会促进我们对他们竞争环境的理解。通常居住在鼻腔中的微生物财团可能很难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然很差。为了鉴定与MRSA定殖的较低风险相关的微生物物种，我们建议在明确定义的受试者队列中前瞻性地表征人类纳雷斯微生物群。一项主动筛查鼻MRSA殖民住院患者的计划是VHA国家努力控制医院退伍军人的MRSA的一部分，并提供了一个以纵向方式收集样本的机会，显然将人定义为非携带者，持久携带者或间歇性携带者或间歇性载体，并确定这些组之间的差异。我们将使用基于创新的DNA序列的技术（16S rRNA宏基因组学），将这些数据与MRSA的定殖和感染相关联，全面确定纵向收集的标本中的鼻膜微生物群。我们对细菌种群之间复杂相互作用的理解才刚刚开始，并且可能导致可以利用的新策略来改善人类健康。可能性包括开发益生菌疗法，鉴定由MRSA抑制性儿子产生的细菌毒素，可用于防止纳雷斯或其他身体部位以防止定殖，并合成细菌蛋白的小分子同源物，这些分子可能可作为全身性抗细菌。