Defined microbial communities to prevent and eradicate infection by AMR pathogens

定义微生物群落以预防和根除 AMR 病原体感染

• 批准号: 10583468
• 负责人: ROBERT A BRITTON
• 金额: $ 56.87万
• 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/10583468
• 关键词: Accounting; Acute; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Back; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Bacteriophages; Cause of Death; Cessation of life; Clinical Trials; Clostridium difficile; Communicable Diseases; Communities; Diagnosis; Diet; Disease; Drug resistance; Enterobacteriaceae; Escherichia coli; Escherichia coli Infections; Exposure to; Extended-spectrum β-lactamase; Focal Infection; Goals; Growth; Health Benefit; Hospitals; Human; Human Microbiome; Human body; In Vitro; Individual; Infection; Infection prevention; Inflammation; Intervention; Intestines; Learning; Lytic; Medical Care Costs; Metabolic; Methods; Microbe; Microbial Physiology; Mucous Membrane; Nutritional; Organoids; Outpatients; Pathogenesis; Patients; Persons; Pharmaceutical Preparations; Pneumonia; Population Heterogeneity; Predisposition; Prevention strategy; Probiotics; Property; Public Health; Recurrence; Resistance; Risk; Sampling; Site; Surface; Testing; Therapeutic; United States; Urinary tract infection; Uropathogen; Vagina; Virulence; Work; carbapenem resistance; clinically relevant; colonization resistance; combat; commensal bacteria; commensal microbes; design; dysbiosis; environmental change; experimental study; fecal transplantation; gastrointestinal; gut microbiome; gut microbiota; healthcare-associated infections; human microbiota; human tissue; innovation; metabolomics; microbial; microbial community; microbiome; microbiota; mouse model; multi-drug resistant pathogen; novel; opportunistic pathogen; pathobiont; pathogen; pathogenic Escherichia coli; pathogenic bacteria; preservation; pressure; prevent; recurrent infection; success; synergism; tissue culture; transmission process

Project Summary Before the discovery of antibiotics, infectious diseases were the three leading causes of death in the United States and constituted nearly 50% of the deaths annually. Today only one infectious disease, pneumonia, is among the top 10 causes of death in the US, largely due to the success of antibiotics in treating bacterial infections. Unfortunately, the public health benefits provided by antibiotics are at serious risk due to the emergence of antibiotic resistant bacteria, an inevitable consequence of the evolutionary pressure exerted on bacteria by these drugs. Eventually the bacterial pathogens we hope to keep at bay will become resistant to all clinically relevant antibiotics, plunging humans back into a pre-antibiotic world in which infectious disease is the leading cause of death. Therefore, we need to find innovative, and rapidly implementable, ways to reduce or supplement antibiotics to preserve their utility in controlling bacterial infections. Many bacterial pathogens, termed pathobionts, reside within the human microbiota in the absence of disease and only instigate pathogenesis after disruption of the microbial community driven by abrupt environmental changes such as acute inflammation. While there is general acceptance that the commensal microbes provide pathogen colonization resistance and suppression of pathobiont virulence in a healthy state, the mechanistic understanding for how they provide these benefits is lacking. In this project, we explore using the human microbiome to identify ecological principles that allow for the design and implementation of microbial communities that suppress bacterial pathogens. We have selected Clostridioides difficile and extraintestinal pathogenic E. coli (ExPEC) as the two main pathogens to study as they are deemed antibiotic resistance threats by the CDC and necessitate millions of antibiotic prescriptions each year. Even with antibiotic treatment, recurrent infections with both of these pathogens is common, and there is currently a lack of long-lasting preventative strategies. Using a novel method to simplify human microbiome communities and advanced in vitro human tissue culture and humanized murine models, we seek to identify key microbial consortia for suppressing these pathogens. We ultimately expect to optimize a small number of defined microbial communities that can be used to eradicate or prevent these infections in people.

项目摘要 在发现抗生素之前，传染病是曼联的三个主要死亡原因 各州并占每年死亡的近50％。今天，只有一种传染病是肺炎 在美国的十大死亡原因中，主要是由于抗生素在治疗细菌方面的成功 感染。不幸的是，由于 抗生素耐药细菌的出现，这是施加进化压力的必然结果 这些药物的细菌。最终，我们希望保持海湾的细菌病原体将对所有人抗拒 临床上相关的抗生素，将人类陷入抗生素的世界中，传染病是 死亡的主要原因。因此，我们需要找到降低或可快速实施的方法来减少或 补充抗生素，以保留其在控制细菌感染方面的效用。许多细菌病原体， 称为病原体，在没有疾病的情况下居住在人类微生物群中 被突然环境变化驱动的微生物群落破坏后的发病机理，例如急性 炎。虽然普遍接受共生微生物提供病原体定殖 在健康状态下对病原体毒力的抗性和抑制 他们提供了这些好处。在这个项目中，我们探索使用人类微生物组来识别 生态原则允许抑制微生物群落的设计和实施 细菌病原体。我们已经选择了梭状芽胞杆菌艰难梭菌和肠外致病性大肠杆菌（Expec） 疾病预防控制中心认为两种主要病原体被认为是抗生素耐药性威胁 每年数百万抗生素处方。即使接受抗生素治疗，这两种复发感染 这些病原体很常见，目前缺乏长期的预防策略。使用小说 简化人类微生物组群落和进步的体外人体组织培养和人性化的方法 鼠模型，我们试图识别抑制这些病原体的关键微生物联盟。我们最终 期望优化可用于根除或防止的少数定义的微生物群落 这些感染者。