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

• 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
• 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

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.

整体项目总结 用抗生素控制细菌感染的能力一直是最重要的公共卫生之一 人类历史上的进步。在发现抗生素和疫苗之前，传染病是 主要死因，仅在美国就占死亡人数的近50%。现在，传染病作为一种 死亡原因勉强排在前十名，我们现在把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。归根结底，我们开发新抗生素的能力比 病原体的出现已经失败，许多科学家预计我们将经历一个回到抗生素出现前的时代 我们不能治疗现在很容易治愈细菌感染的疾病。因此，新奇的、非抗生素的 控制细菌感染的方法是必需的，也需要探索。这次会议的主题是 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学原理以及 使用噬菌体精准清除细菌病原体。这两种方法都有优势 抗生素的使用，因为它们使本地微生物群基本完好无损，避免了 有益的微生物以及抗菌剂所针对的病原体。我们提出了三个项目， 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战略。项目1.发现和机械论 了解噬菌体在宿主粘膜表面的活性和协同作用。项目2.定义的微生物 预防和根除具有抗生素耐药性的病原体感染。项目3.鼻腔微生物 联盟与抗药性细菌作斗争。我们预计执行这些措施会产生两个主要结果 项目。首先，我们希望定义和理解对微生物至关重要的生态学原理 群落和噬菌体起到控制粘膜表面病原体的作用。第二，我们希望 已经确定了可用于人类临床测试的可操作的噬菌体和微生物群落 在项目期结束时进行试验。总而言之，这些项目将利用 粘膜表面，在现代医学之前就已经存在了几千年，随着我们进入下一个时代 以微生物为基础的疗法。