Spatiotemporal Distribution of Oxygen in Biofilm Infections

生物膜感染中氧气的时空分布

基本信息

批准号：
8691938
负责人：
PHILIP S STEWART
金额：
$ 29.62万
依托单位：
MONTANA STATE UNIVERSITY - BOZEMAN
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8691938
关键词：
Aerobic Air Animal Model Antibiotic susceptibility Antibiotics Bacteria Behavior Biocompatible Materials Cessation of life Chronic Cystic Fibrosis Data Dependence Development Diabetic Foot Ulcer Diffusion Engineering Experimental Models Future Gases Goals Growth Health Hyperbaric Oxygenation In Vitro Infection Lead Liquid substance Lung Magnetic Resonance Magnetic Resonance Imaging Maps Measurement Medical Device Microbe Microbial Biofilms Microelectrodes Microscopy Modeling Outcome Oxygen Oxygen Consumption Oxygen saturation measurement Pathogenesis Phagocytes Pneumonia Process Property Pulmonology Respiration Role Science System Techniques Technology Tissues Work Wound Healing Wound Infection antimicrobial chemotherapy chronic rhinosinusitis improved innovation mathematical model microbial model development neutrophil novel novel diagnostics novel therapeutic intervention oxygen microelectrode research study response spatiotemporal tissue oxygenation tissue processing wound

项目摘要

DESCRIPTION (provided by applicant): The overall goal of this project is to develop the first mathematical models of chronic biofilm infection that integrate processes from both host and microbe. A special focus will be the spatiotemporal distribution of oxygen which we hypothesize is critical to the persistence of the infection. Oxygen concentration is important for host healin, clearance of bacteria by neutrophils, and microbial growth and antibiotic susceptibility. Mathematical model development will occur in parallel with experimental measurements of oxygen distributions in novel in vitro biofilm models using microelectrodes and 19F magnetic resonance imaging oximetry. Specific aims of this project are to: 1) Derive integrated mathematical models for cystic fibrosis lung and chronic wound biofilm infection and characterize model behaviors including diffusion properties of heterogeneous reactive biomaterials, bistable outcomes, hysteresis, and responses to perturbations such as hyperbaric oxygen therapy and antimicrobial chemotherapy, and 2) Develop in vitro experimental models of biofilm-infected lung or wound tissues and apply experimental techniques to map spatiotemporal distributions of oxygen in these systems. The mathematical models will describe oxygen dynamics during biofilm infection by incorporating these processes: tissue delivery and host respiration of oxygen, air-liquid gas exchange, biofilm consumption of oxygen, bacterial growth and death, neutrophil invasion and oxygen utilization, and oxygen-dependence of the antimicrobial efficacy of phagocytes and antibiotics. The model is expected to predict the spatiotemporal distribution of oxygen in a biofilm-infected tissue and the persistence of the infection. The development of MRI oximetry for these systems is innovative and paves the way for the application of this technique in animal models in future work. A strong interdisciplinary team of mathematicians, engineers, and four MDs combine expertise with modeling in heterogeneous biological materials including biofilms, biofilm science and technology, magnetic resonance microscopy, wound healing, animal models of biofilm infection, tissue oxygenation, and cystic fibrosis pulmonology.

描述（由申请人提供）：该项目的总体目标是开发第一个整合宿主和微生物过程的慢性生物膜感染数学模型。特别关注的是氧气的时空分布，我们假设这对于感染的持续存在至关重要。氧气浓度对于宿主愈合、中性粒细胞清除细菌、微生物生长和抗生素敏感性很重要。数学模型的开发将与使用微电极和 19F 磁共振成像血氧测定法对新型体外生物膜模型中的氧气分布进行实验测量同时进行。该项目的具体目标是：1）推导出囊性纤维化肺和慢性伤口生物膜感染的综合数学模型，并表征模型行为，包括异质反应性生物材料的扩散特性、双稳态结果、滞后以及对高压氧治疗和抗菌化疗，2) 开发生物膜感染的肺或伤口组织的体外实验模型，并应用实验技术来绘制这些系统中氧气的时空分布。数学模型将通过结合以下过程来描述生物膜感染期间的氧动力学：氧气的组织输送和宿主呼吸、空气-液体气体交换、生物膜的氧气消耗、细菌生长和死亡、中性粒细胞入侵和氧气利用以及细菌的氧气依赖性。吞噬细胞和抗生素的抗菌功效。该模型有望预测生物膜感染组织中氧气的时空分布以及感染的持续性。这些系统的 MRI 血氧测定法的开发具有创新性，为该技术在未来工作中动物模型中的应用铺平了道路。由数学家、工程师和四名医学博士组成的强大跨学科团队将专业知识与异质生物材料建模相结合，包括生物膜、生物膜科学与技术、磁共振显微镜、伤口愈合、生物膜感染动物模型、组织氧合和囊性纤维化肺病学。