Nasal carriage of S. aureus: host-pathogen interactions

金黄色葡萄球菌的鼻携带：宿主-病原体相互作用

基本信息

批准号：
7736782
负责人：
ALEXANDER MICHAEL COLE
金额：
$ 30.34万
依托单位：
UNIVERSITY OF CENTRAL FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-12-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7736782
关键词：
Affect Anterior nares Anti-Bacterial Agents Antibiotic Resistance Antibiotics Apical Bacteria Biological Biological Markers Chronic Clinical Development Disease Epithelial Epithelial Cells Fright Host Defense Human Immunologist In Vitro Individual Integration Host Factors Iron Lactoferrin Link Liquid substance Microbial Biofilms Molecular Mucous Membrane Muramidase Nasal Epithelium Nose Nosocomial Infections Peptides Pharmaceutical Preparations Pilot Projects Predisposing Factor Proteins Proteomics Public Health Research Personnel Resistance Role Shapes Siderophores Source Staphylococcus aureus Structure of mucous membrane of nose Study models Surface Testing Time Work antimicrobial base comparative in vivo inhibitor/antagonist insight interdisciplinary approach killings lipocalin 1 methicillin resistant Staphylococcus aureus novel novel strategies overexpression pathogen polypeptide prevent programs protein expression reconstitution research study resistant strain

项目摘要

Nasal carriage of Staphylococcus aureus (SA) is a common factor that predisposes individuals to severe nosocomial infections, and acts as an important reservoir for harboring and spreading resistant strains. The disorder affects nearly a quarter of apparently healthy people and its molecular and cellular bases are unknown. Experiments from our pilot project revealed that SA nasal carriage may be due to impaired innate antimicrobial activity of nasal fluid. The protein expression levels of a major host defense polypeptide, lipocalin-1 (a scavenger of bacterial siderophores), was found to be reduced in human nasal fluid from donors whose nasal passageways were colonized by SA. In antibacterial studies, lipocalin-1 worked in concert with lysozyme to kill SA in vitro. Most importantly, lipocalin-1 could restore the intrinsic anti-SA activity of non-carrier nasal fluid selectively depleted of cationic polypeptides, and the restorative activity could be abolished by the addition of iron. In the aggregate, our findings clearly suggest an important correlation of lipocalin-1 deficiency with SA carriage. We hypothesize that 1) the expression of lipocalin-1 is dysregulated in the nasal mucosa of SA carriers, contributing to the progressive colonization of SA, 2) correcting the lipocalin-1 deficiency will reconstitute the antimicrobial activity of SA carrier nasal fluid against isolates of SA, and 3) SA augments the epithelial expression of lipocalin-1 and other host defense molecules, which contributes to preferential colonization of SA on carrier mucosa as compared with non- carrier mucosa. To test these hypotheses, we will: 1) Characterize the biological role of lipocalin-1 in SA nasal carriage, 2) Examine the influence of bacterial and host factors on the expression and anti-SA activity of lipocalin-1, and 3) Examine the contribution of human nasal epithelium to SA colonization. Our proposed studies represent a biologically relevant approach to identify and link causative factors of human airway disease (cationic polypeptide antimicrobials) with their effects (SA nasal carriage). Relevance to Public Health: SA carriage is of increasing clinical importance because hospital-acquired infections are commonly spread by people who carry antibiotic-resistant SA in their nostrils. Our studies will characterize factors responsible for SA carriage, and will continue to develop a very useful and natural model for studying the interactions of bacteria with a readily accessible mucosal surface in humans.

金黄色葡萄球菌（SA）的鼻载载是一个常见因素，使人易于严重医院感染，是藏有和扩散抗性菌株的重要储层。这疾病影响近四分之一的看似健康的人，其分子和细胞基础是未知。我们的飞行员项目的实验表明，鼻鼻携带可能是由于先天而受损的鼻液的抗菌活性。主要宿主防御多肽的蛋白质表达水平，发现Lipocalin-1（细菌铁载体的清道夫）在人类鼻液中降低了 SA的鼻通道的捐助者被殖民。在抗菌研究中，lipocalin-1在与溶菌酶在体外杀死SA的音乐会。最重要的是，Lipocalin-1可以恢复固有的抗SA 非载体鼻液的活性选择性地耗尽了阳离子多肽和恢复活性可以通过添加铁来消除。总体而言，我们的发现显然暗示了一个重要的 Lipocalin-1缺乏症与SA运输的相关性。我们假设1）Lipocalin-1的表达为 SA载体的鼻粘膜失调，导致SA的进行性殖民化，2）纠正Lipocalin-1缺乏症将重建SA载体鼻液的抗菌活性 SA的分离株和3）SA增强Lipocalin-1和其他宿主防御的上皮表达与非 - 载体粘膜。为了检验这些假设，我们将：1）表征Lipocalin-1在SA中的生物学作用鼻携带，2）检查细菌和宿主因子对表达和抗SA活性的影响 Lipocalin-1和3）检查人鼻上皮对SA定植的贡献。我们提出的研究代表了一种与生物学相关的方法，用于识别和联系人类气道的病因因素疾病（阳离子多肽抗菌剂）及其作用（Sa鼻式运输）。与公共卫生有关：SA运输的临床重要性越来越重要感染通常是由鼻孔中携带抗生素耐药的人传播的。我们的研究将表征负责SA运输的因素，并将继续开发一个非常有用且自然的模型用于研究细菌与人类易于获得的粘膜表面的相互作用。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Phylogenetic relationships among Staphylococcus species and refinement of cluster groups based on multilocus data.

DOI：
10.1186/1471-2148-12-171
发表时间：
2012-09-06
期刊：
BMC evolutionary biology
影响因子：
3.4
作者：
Lamers RP;Muthukrishnan G;Castoe TA;Tafur S;Cole AM;Parkinson CL
通讯作者：
Parkinson CL

Longitudinal genetic analyses of Staphylococcus aureus nasal carriage dynamics in a diverse population.

DOI：
10.1186/1471-2334-13-221
发表时间：
2013-05-16
期刊：
BMC infectious diseases
影响因子：
3.7
作者：
Muthukrishnan G;Lamers RP;Ellis A;Paramanandam V;Persaud AB;Tafur S;Parkinson CL;Cole AM
通讯作者：
Cole AM

Suppression of innate immunity by a nasal carriage strain of Staphylococcus aureus increases its colonization on nasal epithelium.

金黄色葡萄球菌鼻携带菌株对先天免疫的抑制增加了其在鼻上皮上的定植。