Genome-Wide Screening for Enteric Colonization Factors in Carbapenem-Resistant ST258 Klebsiella pneumoniae

Author:

Jung Hea-Jin1,Littmann Eric R.2,Seok Ruth1,Leiner Ingrid M.1,Taur Ying23,Peled Jonathan4,van den Brink Marcel4,Ling Lilan2,Chen Liang5,Kreiswirth Barry N.5,Goodman Andrew L.6,Pamer Eric G.123

Affiliation:

1. Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York, USA

2. Center for Microbes, Inflammation, and Cancer, Molecular Microbiology Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York, USA

3. Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

4. Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA

5. Public Health Research Institute, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, New Jersey, USA

6. Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, Connecticut, USA

Abstract

Klebsiella pneumoniae is a common cause of bloodstream infections in immunocompromised and hospitalized patients, and over the last 2 decades, some strains have acquired resistance to nearly all available antibiotics, including broad-spectrum carbapenems. The U.S. Centers for Disease Control and Prevention has listed carbapenem-resistant K. pneumoniae (CR -Kp ) as an urgent public health threat. Dense colonization of the intestine by CR -Kp and other antibiotic-resistant bacteria is associated with an increased risk of bacteremia. Reducing the density of gut colonization by CR -Kp is likely to reduce their transmission from patient to patient in health care facilities as well as systemic infections. How CR -Kp expands and persists in the gut lumen, however, is poorly understood. Herein, we generated a highly saturated mutant library in a multidrug-resistant K. pneumoniae strain and identified genetic factors that are associated with dense gut colonization by K. pneumoniae . This study sheds light on host colonization by K. pneumoniae and identifies potential colonization factors that contribute to high-density persistence of K. pneumoniae in the intestine.

Funder

HHS | National Institutes of Health

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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