Host-Pathogen Interactions in Staphylococcus aureus Infection (pp 312-313)

金黄色葡萄球菌感染中宿主与病原体的相互作用（第 312-313 页）

基本信息

批准号：
9045844
负责人：
RICHARD M CAPRIOLI
金额：
$ 28.5万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9045844
关键词：
Abscess Anatomy Anterior nares Antimicrobial Resistance Bacteria Beds Biological Process Biology Blood Circulation Catalysis Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Communities Data Disease Elements Environment Enzymes Future Generations Growth Heart Hematoxylin and Eosin Staining Method Heterogeneity Histocompatibility Testing Histologic Homeostasis Human Hydrogels Image Immune Immune response Immunity Infection Intervention Kidney Laboratories Lesion Light Liver Mass Spectrum Analysis Metals Methods Microbial Biofilms Microscopy Modeling Modern Medicine Molecular Molecular Models Necrosis Nutrient Nutritional Optics Organ Oxidative Stress Population Population Heterogeneity Process Proliferating Proteins Proteomics Reporting Research Resolution Resources Signal Transduction Site Staining method Stains Staphylococcus aureus Techniques Technology Testing Therapeutic Therapeutic Agents Time Tissues Transition Elements United States Universities Virulence Factors antimicrobial bacterial genetics clinically relevant cofactor disorder prevention drug resistant bacteria experience human disease infectious disease treatment killings macrophage microbial microbial community molecular marker molecular modeling mouse model neutrophil new therapeutic target novel novel therapeutics pathogen protein distribution protein expression renal abscess response small molecule

项目摘要

Bacterial pathogens are rapidly gaining resistance to antimicrobial therapeutics undermining the ability of modern medicine to treat such infections [1,2]. The Centers for Disease Control and Prevention reported over 2 million people in the United States become infected with drug-resistant bacteria annually, causing at least 23,000 deaths [3]. In light of such reports, the need to identify and study novel targets for antimicrobial intervention using emerging analytical technologies is paramount for the future successful treatment of infectious diseases. One potential target for antimicrobial therapeutics involves transition metal homeostasis at the pathogen-host interface [4,5]. Metals are an essential component of biological function for all cells. It is estimated that 30-45% of all enzymes utilize a transition metal cofactor to enhance catalysis and reactivity [6,7]. Therefore, bacterial pathogens proliferating within a host must obtain metals to survive and grow, causing disease. In response, hosts seek to sequester these elements from pathogens, a process known as nutritional immunity [4,8]. With a more detailed understanding of host mechanisms of metal sequestration and bacterial mechanisms of metal scavenging, novel therapeutic targets can be discovered. S. aureus is a Gram-positive pathogen that commensally colonizes the anterior nares of an estimated 25% of the human population [9]. To cause disease, S. aureus breaches the initial site of infection and enters the bloodstream where it can cause infectious lesions on virtually any organ [10]. A hallmark of these purulent infectious foci, called abscesses, is the recruitment of host immune cells, including neutrophils and macrophages, which generate oxidative stress in an attempt to kill the pathogen [11,12]. Abscess formation has been studied extensively using histologically methods [10,13,14]; however, a molecular understanding of organ-specific heterogeneity of bacterial virulence factor expression and host response is not yet understood.

细菌病原体正在迅速获得对抗菌治疗药的抗药性现代医学治疗这种感染的能力[1,2]。疾病控制与预防中心据报道，美国超过200万人每年感染了耐药细菌，造成至少23,000人死亡[3]。鉴于此类报告，需要识别和研究新的目标使用新兴分析技术的抗菌干预对于未来成功至关重要治疗传染病。抗菌治疗剂的一个潜在靶标涉及过渡金属病原体宿主界面的稳态[4,5]。金属是生物学功能的重要组成部分所有细胞。据估计，所有酶的30-45％都利用过渡金属辅因子来增强催化和反应性[6,7]。因此，在宿主内增殖的细菌病原体必须获得生存的金属，并且成长，导致疾病。作为回应，主机试图从病原体中隔离这些元素，这是一个过程称为营养免疫[4,8]。对金属的宿主机制有更详细的了解可以发现金属清除，新型治疗靶标的隔离和细菌机制。金黄色葡萄球菌是一种革兰氏阳性病原体，在估计25％的前鼻孔中共同定居人口[9]。为了引起疾病，金黄色葡萄球菌违反了最初的感染部位并进入血液几乎可以在任何器官上引起感染性病变[10]。这些脓性的标志传染灶，称为脓肿，是宿主免疫细胞的募集，包括中性粒细胞和巨噬细胞产生氧化应激以杀死病原体[11,12]。脓肿的形成已经使用组织学方法进行了广泛的研究[10,13,14]；但是，对分子的理解细菌毒力因子表达和宿主反应的器官特异性异质性尚不清楚。