Microbiome Discovery and Mechanisms to Combat Antibiotic Resistance at Mucosal Surfaces

微生物组的发现和对抗粘膜表面抗生素耐药性的机制

基本信息

批准号：
10357964
负责人：
ROBERT A BRITTON
金额：
$ 240.27万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10357964
关键词：
Active Sites Address Anti-Bacterial Agents Antibiotic Resistance Antibiotics Bacteria Bacterial Antibiotic Resistance Bacterial Infections Bacteriophages Benign Biology COVID-19 pandemic Cause of Death Cessation of life Chemical Structure Chemicals Chronic Clinic Clinical Clinical Trials Clostridium difficile Combating Antibiotic Resistant Bacteria Communicable Diseases Communities Complex Development Disease Drug resistance ESKAPE pathogens Ecology Effectiveness Environment Enzymes Equilibrium Failure Gastrointestinal tract structure Genes Genetic Genitourinary system Health Horizontal Gene Transfer Human Incentives Individual Infection Infection prevention Lead Life Measures Methods Modeling Modern Medicine Mucous Membrane Mutation Nasal Epithelium Nature Nose Occupations Organoids Outcome Patients Pharmaceutical Preparations Planet Earth Prevention strategy Process Property Public Health Recording of previous events Research Resistance Resistance development Scientist Streptococcus pneumoniae Surface Testing Therapeutic Transplantation Uncertainty Vaccines Validation Viral Virus Work antagonist antibiotic resistant infections antimicrobial base beneficial microorganism clinical practice combat drug resistant pathogen emerging pathogen experience fecal transplantation fighting gut colonization high risk innovation methicillin resistant Staphylococcus aureus microbial microbial community microbiome microbiota mucosal site nasal microbiota novel novel therapeutics pandemic disease pathobiont pathogen pathogenic Escherichia coli pathogenic bacteria pre-clinical pressure prevent programs prophylactic repository resistant strain synergism tool transmission process

项目摘要

Overall Project Summary The ability to control bacterial infections with antibiotics has been one of the most important public health advancements in human history. Before the discovery of antibiotics and vaccines, infectious disease was the leading cause of death and constituted nearly 50% of deaths in the US alone. Now, infectious diseases as a cause of death barely makes the top ten and we now treat most bacterial infections as a nuisance rather than life-threatening diseases. Unfortunately, this is rapidly changing with the emergence of antibiotic resistant bacterial pathogens. Ultimately, our ability to develop new antibiotics faster than resistance amongst pathogens emerges has failed and many scientists expect we will experience a return to a pre-antibiotic era in which we cannot treat what are now easy to cure bacterial infections. Therefore, novel, non-antibiotic approaches to controlling bacterial infections are required and need to be explored. The main theme of the BCM-CARBIRU is to use microbiome-based approaches to control bacterial infections at mucosal surfaces. We will investigate ecological principles of microbial community inhibition of pathogen colonization as well as the use of bacteriophage for precision elimination of bacterial pathogens. Both approaches have advantages over the use of antibiotics in that they leave the native microbiome largely intact, avoiding the elimination of beneficial microbes along with the pathogens targeted by antimicrobials. We propose three projects, supported by two scientific cores and the administrative core, to explore and optimize microbiome-based strategies for the prevention and treatment of bacterial infections. Project 1. Discovery and mechanistic understanding of phage activity and synergism at host mucosal surfaces. Project 2. Defined microbial communities to prevent and eradicate infection by antibiotic resistant pathogens. Project 3. Nasal microbial consortia combat antibiotic-resistant bacteria. We expect two main outcomes from the execution of these projects. First, we expect to define and understand the ecological principles that are key for microbial communities and bacteriophage to function to control pathogens at mucosal surfaces. Second, we expect to have identified actionable phage and microbial communities that will be available for testing in human clinical trials at the end of the project periods. Together, these projects will capitalize on protective measures at the mucosal surface, which have existed for millennia prior to modern medicine, as we enter the next era of microbiome-based therapies.

项目总体概要使用抗生素控制细菌感染的能力一直是最重要的公共卫生问题之一人类历史的进步。在抗生素和疫苗发现之前，传染病是最常见的疾病是导致死亡的主要原因，仅在美国就占死亡人数的近 50%。现在，传染病作为死亡原因勉强进入前十名，我们现在将大多数细菌感染视为一种滋扰，而不是危及生命的疾病。不幸的是，随着抗生素耐药性的出现，这种情况正在迅速改变细菌病原体。最终，我们开发新抗生素的速度快于抗生素耐药性的速度病原体的出现已经失败，许多科学家预计我们将回到前抗生素时代我们无法治疗现在很容易治愈的细菌感染。因此，新型、非抗生素需要并需要探索控制细菌感染的方法。该剧的主题是 BCM-CARBIRU 将使用基于微生物组的方法来控制粘膜表面的细菌感染。我们将研究微生物群落抑制病原体定植的生态原理以及使用噬菌体精确消除细菌病原体。两种方法各有优点与使用抗生素相比，它们使天然微生物群基本保持完整，避免了消除有益微生物以及抗菌药物针对的病原体。我们提出三个项目，在两个科学核心和行政核心的支持下，探索和优化基于微生物组的预防和治疗细菌感染的策略。项目1.发现与机制了解宿主粘膜表面的噬菌体活性和协同作用。项目2.定义的微生物社区预防和根除抗生素耐药病原体的感染。项目3.鼻腔微生物联盟对抗抗生素耐药细菌。我们预计这些措施的执行将产生两个主要成果项目。首先，我们期望定义和理解对于微生物至关重要的生态原理群落和噬菌体发挥控制粘膜表面病原体的作用。其次，我们期望已经确定了可用于人类临床测试的可操作噬菌体和微生物群落项目期结束时进行试验。这些项目将共同利用保护措施粘膜表面，在现代医学之前就已经存在了几千年，当我们进入下一个时代时基于微生物组的疗法。