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Investigating the Role of Mechanical Forces in the Catheter-Related Pathogenesis of Staphylococci, From Adhesion to Biofilm Formation.

机译：研究机械力在葡萄球菌的导管相关发病机制中的作用，从粘附到生物膜形成。

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摘要

Intravenous catheter related blood stream infections (CRBSI) are the major cause of healthcare-associated infections to date, and result in both increased morbidity and mortality in patients with undeveloped and compromised immunity, as well as a significant cost burden on health systems. Staphylococcus epidermidis and S. aureus are both normal inhabitants of human skin and mucous membranes and also are the organisms most significantly cultured from these infections. CRBSIs from Staphylococci can be extremely harmful if left untreated even for a mater of a few days. These infections can result in serious conditions such as native valve endocarditis, and even bacteremia sepsis.;The pathogenesis is complex, involving multicellular choreography and host immune evasion, however it is well accepted that two key steps are (i) adhesion to the catheter lumen by planktonic cells and (ii) subsequent biofilm formation to establish a stable source of bacterial cells for infection. Adhesion is largely mediated by surface exposed adhesins, targeting a number of soluble host plasma proteins and extracellular matrix components. Biofilm formation has been shown to occur through a number of pathways, however a commonly occurring theme is through secretion of polysaccharide intracellular adhesin (PIA) matrix, driven by expression of the chromosomal icaADBC operon.;We have developed a novel toolset using microfluidics to recapitulate the pathogenic environment incorporating clinically relevant fluid shear stress. Using this microfluidic assay, we show that shear stress from fluid flow modulated the pathogenic potential of S. epidermidis, both in terms of increased adhesive capability as well as the induction of biofilm formation is normally quiescent strains. Further, we have developed a high-throughput, multidimensional microfluidic assay incorporating functional adhesive protein microarrays and large scale microfluidic networks. This assay will be used to generate quantitative `pathogenicity landscapes' in Staphylococci, towards the identification of novel therapeutic targets to mitigate and treat device related infections.
机译：迄今为止，静脉导管相关的血流感染（CRBSI）是与医疗保健相关的感染的主要原因，并且会导致免疫力不完善和受损的患者的发病率和死亡率增加，并且给卫生系统带来巨大的成本负担。表皮葡萄球菌和金黄色葡萄球菌都是人类皮肤和粘膜的正常居民，也是从这些感染中培养出来的最重要的生物。如果不治疗，葡萄球菌的CRBSI可能会极为有害，甚至持续数天。这些感染可能导致严重的疾病，例如天然瓣膜心内膜炎，甚至是败血症;败血症的发病机制很复杂，涉及多细胞编排和宿主免疫逃逸，但是众所周知，两个关键步骤是（i）粘附于导管腔（ii）随后的生物膜形成，以建立稳定的细菌细胞感染源。粘附主要由表面暴露的粘附素介导，其靶向许多可溶性宿主血浆蛋白和细胞外基质成分。生物膜的形成已通过多种途径发生，但是普遍发生的主题是通过多糖ICAADBC操纵子的表达驱动多糖细胞内粘附素（PIA）基质的分泌。我们已经开发出了一种使用微流控技术进行概括的新型工具集具有临床相关流体剪切应力的致病环境。使用这种微流体测定法，我们表明从流体流动的剪切应力调节表皮葡萄球菌的致病潜力，就增加的粘附能力以及生物膜形成的诱导而言，通常是静态菌株。此外，我们已经开发了一种高通量，多维微流体分析方法，该方法结合了功能性粘附蛋白微阵列和大规模微流体网络。该测定法将用于在葡萄球菌中产生定量的“致病性景观”，以鉴定减轻和治疗设备相关感染的新型治疗靶标。

著录项

  • 作者

    Weaver, Westbrook McConnell.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Engineering Biomedical.;Biology Microbiology.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 118 p.
  • 总页数 118
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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