Elucidating the Role of Biofilm-Forming Bacteria in Nephrolithiasis

阐明生物膜形成细菌在肾结石中的作用

• 批准号: 10740776
• 负责人: Kymora B Scotland
• 金额: $ 17.11万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10740776
• 关键词: 3-Dimensional; Affect; Bacteria; Behavior; Biophysics; Calcium; Calcium Oxalate; Calcium ion; Calculi; Cells; Charge; Clinical; Collaborations; Complement; Crystallization; DNA; Data; Deoxyribonucleases; Deposition; Development; Diet; Disease; Environment; Escherichia coli; Etiology; Fluorescence; Fluorescence Microscopy; Fluorescent in Situ Hybridization; Foundations; Funding; Future; Genetic; Genetic Techniques; Goals; Growth; Hydration status; Image; In Situ; In Vitro; Infection; Kidney; Kidney Calculi; Knowledge; Learning; Link; Machine Learning; Mediating; Mentors; Mentorship; Methods; Microbe; Microbial Biofilms; Microbiology; Microscopy; Modeling; Molecular; Molecular Biology; Molecular Genetics; Mutation; Nature; Nephrolithiasis; Organelles; Pathogenesis; Pathway interactions; Patients; Physiological; Physiology; Pilum; Play; Polymers; Population; Process; Productivity; Pseudomonas; Pseudomonas aeruginosa; Publications; Raman Spectrum Analysis; Reaction; Research; Research Personnel; Resolution; Rodent Model; Roentgen Rays; Role; Sampling; Scientist; Stents; Surface; Surgeon; Techniques; Testing; Training; Urinary system; Urinary tract; Urinary tract infection; Urine; Urology; Uropathogen; Work; appendage; biomineralization; bioprinting; career; cell motility; comparison control; cost; cost estimate; experience; experimental study; extracellular; fabrication; high resolution imaging; imaging modality; improved; in vitro Model; in vivo; insight; kidney cell; microbial; model organism; next generation sequencing; novel; skills; tool; urinary

TITLE: Elucidating the Role of Biofilm-Forming Bacteria in Nephrolithiasis PROJECT SUMMARY/ ABSTRACT Kidney stone disease is common, affecting 11% of the US population. However, the pathogenesis of kidney stones is still not well understood. While 10% of stones are known to be infectious, calcium-based stones, which make up 80% of stones, have not previously been shown to associate with bacteria. However, recent publications have utilized next-generation sequencing to demonstrate bacterial infestation in calcium stones despite no evidence of prior or concurrent urinary tract infection in those patients. In preliminary work, we found that uropathogenic bacteria trigger increased calcium oxalate crystal growth compared to controls. We hypothesize that bacteria interact with calcium stones and promote the propagation of kidney stones. We further propose that this interaction involves the formation of bacterial biofilm. We will test these hypotheses using three specific aims: 1) To test the hypothesis that uropathogens initiate biofilm formation in stones 2) To test the hypothesis that known surface sensing pathways of Pseudomonas spp. and E coli trigger kidney stone formation and 3) To test the hypothesis that bacteria play an important role in triggering crystallization and crystal aggregation in urine-specific environments using an in vitro three-dimensional kidney model. These aims will be accomplished by utilizing multiple imaging and complementary techniques including Raman spectroscopy and x-ray fluorescence as well as single-cell tracking analyses and molecular genetic techniques to investigate biofilm initiation. This study will provide new insights into the role of bacteria in the propagation of calcium-based kidney stones. It will also facilitate the advancement of my independent biomedical researcher career. I will collaborate with and obtain guidance and tutelage from highly successful, experienced mentors who are committed to my professional development. My research capabilities will be augmented by didactic and hands-on training in microbiology, machine learning, and high-resolution imaging, thus preparing me with the tools necessary to transition to full independence as a surgeon-scientist. Lastly, this funding will allow me to contribute to elucidating the etiology of nephrolithiasis and will directly enable provide the preliminary data for my first R01 application.

标题：阐明形成生物膜的细菌在肾石器中的作用 项目摘要/摘要 肾结石很常见，影响美国人口的11％。但是， 肾结石的发病机理仍然不太了解。众所周知，有10％的石头是 占石头80％的传染性，基于钙的石头，以前尚未显示 与细菌缔合。但是，最近的出版物使用了下一代测序 尽管没有证据表明先前或并发 这些患者的尿路感染。在初步工作中，我们发现肝癌细菌 与对照组相比，触发了草酸钙晶体生长的增加。我们假设这一点 细菌与钙结石相互作用，并促进肾结石的繁殖。我们进一步 提出这种相互作用涉及细菌生物膜的形成。 我们将使用三个特定目的检验这些假设： 1）检验尿道病启动石头生物膜形成的假设 2）检验假说的假设是假单胞菌属的已知表面传感途径。和大肠杆菌 触发肾结石的形成和 3）检验假说，即细菌在触发结晶和 使用体外三维肾脏在尿液特异性环境中的晶体聚集 模型。 这些目标将通过使用多种成像和互补技术来实现 包括拉曼光谱和X射线荧光以及单细胞跟踪分析 和分子遗传技术研究生物膜起始。 这项研究将为细菌在基于钙的传播中的作用提供新的见解 肾结石。这也将促进我的独立生物医学研究人员的进步 职业。我将与高度成功的指导和指导和指导 经验丰富的导师，致力于我的职业发展。我的研究 微生物学，机器的教学和动手培训将增强功能 学习和高分辨率成像，从而为我准备过渡到过渡到的工具 完全独立作为外科医生科学家。最后，这笔资金将使我能够为 阐明肾时期病的病因，并将直接提供初步数据 我的第一个R01应用程序。