Nasal carriage of S. aureus: host-pathogen interactions

鼻腔携带金黄色葡萄球菌（SA）是一种常见的因素，易使个人严重 医院感染，并作为一个重要的水库窝藏和传播耐药菌株。的 疾病影响近四分之一的表面健康的人，其分子和细胞基础是 未知我们的试点项目的实验表明，SA鼻携带可能是由于先天性受损， 鼻液的抗菌活性。主要宿主防御多肽的蛋白质表达水平， 脂质运载蛋白-1（细菌铁载体的清除剂）在人鼻液中被发现减少， 其鼻腔通道被SA定殖的供体。在抗菌研究中，脂质运载蛋白-1在 在体外与溶菌酶协同杀死SA。最重要的是，脂质运载蛋白-1可以恢复内源性抗SA 选择性去除阳离子多肽的非载体鼻液的活性，以及 可以通过添加铁来消除。总的来说，我们的研究结果清楚地表明， 脂质运载蛋白-1缺乏与SA携带的相关性。我们假设：1）脂质运载蛋白-1的表达是 在SA携带者的鼻粘膜中失调，促进SA的进行性定殖，2） 纠正脂质运载蛋白-1缺乏将重建SA载体鼻液的抗微生物活性， SA的分离物，以及3）SA增强脂质运载蛋白-1和其它宿主防御的上皮表达 分子，这有助于SA在载体粘膜上的优先定殖，与非- 粘膜载体为了验证这些假设，我们将：1）表征脂质运载蛋白-1在SA中的生物学作用 2）检测细菌和宿主因素对表达和抗SA活性的影响 和3）检查人鼻上皮对SA定殖的贡献。我们提出的 研究代表了一种生物学相关的方法来识别和联系人类气道疾病的致病因素， 疾病（阳离子多肽抗菌剂）及其影响（SA鼻携带）。 与公共卫生的相关性：SA携带具有越来越重要的临床意义，因为医院获得性 感染通常是由鼻孔中携带抗药性SA人传播的。我们的研究将 描述SA携带的因素，并将继续开发一个非常有用和自然的模型 用于研究细菌与人体易于接触的粘膜表面的相互作用。

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.