Microbial genomics of hospital-associated pathogens

National Human Genome Research Institute

Investigators

Linked publications & trials

Abstract

With a dearth of new classes of antimicrobials in development, hospital infection control is crucial to prevent the rise of intractable multi-drug resistant bacterial and fungal infections. Whole genome sequencing provides a level of resolution that far exceeds traditional typing methods. This high level resolution enables tracking the spread of pathogens within and between hospitals, thus identifying possible weaknesses in existing practices and points of intervention. We aim to use genomic information to model outbreaks, monitor evolution of antibiotic resistance and develop risk assessment strategies. Hospital-acquired infections result in 100,000 deaths per year, and represent a tremendous social cost to patients and their families. My laboratory's mission is to use genomic information to model clusters of bacterial infections and transmissions, monitor evolution of antibiotic resistance and develop risk assessment strategies. Our foundational studies demonstrated that integration of genomic and epidemiological data can yield actionable insights and facilitate the control of nosocomial transmission. We have promoted patient safety at the NIH clinical center through our studies of both carbapenem resistant Klebsiella pneumoniae and Sphingomonas koreensis. We study multiple aspects of the emerging human pathogen Candida auris to inform clinical care, including identifying sites of colonization and genetic diversification on patients. We study transmissions in ongoing hospital outbreaks within the United States in collaboration with colleagues at CDC and others. Together with collaborators we aim to test possible strategies to protect or to decolonize patients.We explore the genetic diversity of Candida auris colonizing patients combining shotgun metagenomic, isolate, and plate metagenomic sequencing. Shotgun metagenomic sequencing reveals both bacterial and fungal pathogens that colonize the skin of residents of nursing homes. Combining genomic data with epidemiological clinical metadata we explore strain sharing within facilities. We developed mouse models to understand the skin colonization of Candida auris to explore both commensalism and colonization resistance. We are exploring how candida auris has adapted as a skin commensal using genetic and in vitro methods. These studies have identified sites of Candida auris colonization and tested strategies used to control colonization in vulnerable patient populations. Our long-term goal is both to promote hospital infection control and to tailor drug strategies to minimize the acquisition of antibiotic resistance. Collaboration among physicians who have expertise in healthcare epidemiology, microbiologists who have expertise in diagnostics, and scientists who have expertise in genomics is critical to take advantage of emerging technologies and translate them into improved patient care.