CK20-004, J. Craig Venter Insitute and Cleveland VA Prevention and Intervention Epicenter

项目摘要/摘要 克雷格·文特尔研究所(JCVI)和克利夫兰退伍军人管理局预防和干预中心的目标 将开发新的干预措施，以防止抗生素耐药性(AR)的定植和传播 导致医院获得性感染(HAI)的细菌，并开发诊断和干预措施以对抗 快速出现的真菌病原体金黄色念珠菌的定植。 拟建的震中将利用我们在全球多家医院的临床合作者网络。 美国在住院急诊护理、门诊和长期护理环境中。此外，这个震中将会 受益于在JCVI管理大型协作多学科项目的十多年经验 例如人类微生物组计划(HMP)、微生物测序中心(MSC)、基因组测序 传染病基因组中心(GCID)，病原功能基因组资源 中心(PFGRC)和Pahema。JCVI(在首席调查员德里克·福茨博士的领导下)有一个 与克利夫兰退伍军人管理局建立了长期的合作关系，在 GSC和GCID中心，以及目前由国防部资助的伤口微生物组项目。 新出现的多药耐药(MDR)使CDC引起的感染的治疗成为细菌的优先事项 (例如，耐碳青霉烯类肠杆菌科细菌、鲍曼不动杆菌、铜绿假单胞菌)和 真菌(例如，金黄色念珠菌)病原体越来越无效，是一个主要的全球卫生问题。我们会 通过创建一个由四个T0期核心项目组成的震中来实现我们的目标 减少AR感染的预防中心方案研究优先事项(核心项目1)，微生物组 (核心项目2)，了解和减少传播(核心项目3)，以及诊断，无症状 新耐药性的殖民和遏制(核心项目4)。具体来说，我们将使用共生菌 或其产品破坏AR细菌引起的生物膜，以减少核心项目1中的感染，保护和 在核心项目2中使用噬菌体恢复鼻腔和肠道微生物群。我们还将减少传播 利用性毛特异性噬菌体和CRISPR靶向消化结合质粒引起的AR 核心项目3中质粒携带的基因。最后，将开发新的诊断和益生菌方法 为了更好地检测和减少新出现的真菌病原体C. Auris在核心项目4。

PROJECT SUMMARY/ABSTRACT The objectives of the J. Craig Venter Institute (JCVI) and Cleveland VA Prevention and Intervention Epicenter are to develop novel interventions that will prevent the colonization and spread of antibiotic resistant (AR) bacteria that cause hospital acquired infections (HAI), and to develop diagnostics and interventions to combat the colonization by the rapidly emerging fungal pathogen Candida auris. The proposed Epicenter will leverage our network of clinical collaborators at multiple hospitals throughout the United States at inpatient acute care, outpatient, and long-term care settings. In addition, this Epicenter will benefit from greater than a decade of experience at JCVI managing large collaborative multidisciplinary projects such as the Human Microbiome Project (HMP), Microbial Sequencing Center (MSC), Genome Sequencing Center (GSC), Genomic Centers for Infectious Disease (GCID), Pathogen Functional Genomics Resource Center (PFGRC) and Pathema. JCVI (under the leadership of Principal Investigator Dr. Derrick Fouts) has a longstanding relationship with the Cleveland VA having collaborated on several AR bacteria projects within the GSC and GCID centers and on a currently funded DoD wound microbiome project. Emerging multidrug resistance (MDR) is making treatment of infections caused by CDC high priority bacterial (e.g., carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa) and fungal (e.g., Candida auris) pathogens increasingly ineffective and is a major global health concern. We will accomplish our goals by the creation of an Epicenter consisting of four Phase T0 Core projects covering the Prevention Epicenters Program Research Priorities of Decreasing AR infections (Core project 1), Microbiome (Core project 2), Understanding and decreasing transmission (Core project 3), and Diagnostics, Asymptomatic colonization and Containment of novel resistance (Core project 4). Specifically, we will use commensal bacteria or their products to disrupt biofilms caused by AR bacteria to decrease infections in Core project 1, protect and restore nasal and gut microbiomes using bacteriophage in Core project 2. We will also reduce the transmission of AR caused by conjugative plasmids by using sex pilus-specific phage and CRISPR-targeted digestion of plasmid-borne genes in Core project 3. And finally, novel diagnostic and probiotic approaches will be developed to enable better detection and reduce asymptomatic colonization by the newly emerging fungal pathogen C. auris in Core project 4.