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

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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.