Microbiome Discovery and Mechanisms to Combat Antibiotic Resistance at Mucosal Surfaces

总体项目摘要 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 人类历史的进步。在发现抗生素和疫苗之前，传染病是人类最常见的疾病。 这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，传染病作为一种 死亡原因几乎没有排在前十位，我们现在把大多数细菌感染视为讨厌的东西，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， 细菌病原体最终，我们开发新抗生素的能力比耐药性更快， 病原体的出现已经失败，许多科学家预计，我们将经历一个前抗生素时代的回归， 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。的主旋律 BCM-CARBIRU是使用基于微生物组的方法来控制粘膜表面的细菌感染。 我们将探讨微生物群落抑制病原体定殖的生态学原理， 使用噬菌体精确消除细菌病原体。两种方法都有优点 抗生素的使用，因为它们在很大程度上保持了原生微生物组的完整性，避免了 有益微生物沿着抗菌剂靶向的病原体。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。发现和机制 理解噬菌体活性和宿主粘膜表面的协同作用。项目2.确定的微生物 社区预防和根除耐抗生素病原体感染。项目3。鼻微生物 抵抗抗药性细菌的联合体。我们预计，这些措施的执行将产生两个主要结果。 项目首先，我们希望定义和理解微生物的关键生态原则， 群落和噬菌体的功能，以控制粘膜表面的病原体。第二，我们希望 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 在项目期结束时进行审判。这些项目将共同利用 粘膜表面，这已经存在了几千年前的现代医学，因为我们进入下一个时代， 基于微生物组的疗法。

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.