Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence

Travis J. Kochan (), Sophia H. Nozick, Aliki Valdes, Sumitra D. Mitra, Bettina H. Cheung, Marine Lebrun-Corbin, Rachel L. Medernach, Madeleine B. Vessely, Jori O. Mills, Christopher M. R. Axline, Julia A. Nelson, Ethan M. VanGosen, Timothy J. Ward, Egon A. Ozer, David Duin, Liang Chen, Barry N. Kreiswirth, S. Wesley Long, James M. Musser, Zackery P. Bulman, Richard G. Wunderink and Alan R. Hauser
Additional contact information
Travis J. Kochan: Laboratory of Respiratory and Special Pathogens, Division of Bacterial, Parasitic, and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration
Sophia H. Nozick: Northwestern University
Aliki Valdes: Northwestern University
Sumitra D. Mitra: Northwestern University
Bettina H. Cheung: Northwestern University
Marine Lebrun-Corbin: Northwestern University
Rachel L. Medernach: Northwestern University
Madeleine B. Vessely: Northwestern University
Jori O. Mills: Northwestern University
Christopher M. R. Axline: Northwestern University
Julia A. Nelson: Northwestern University
Ethan M. VanGosen: Northwestern University
Timothy J. Ward: Northwestern University
Egon A. Ozer: Northwestern University
David Duin: University of North Carolina
Liang Chen: Center for Discovery and Innovation, Hackensack Meridian Health
Barry N. Kreiswirth: Center for Discovery and Innovation, Hackensack Meridian Health
S. Wesley Long: Houston Methodist Hospital Research Institute
James M. Musser: Houston Methodist Hospital Research Institute
Zackery P. Bulman: University of Illinois at Chicago
Richard G. Wunderink: Northwestern University
Alan R. Hauser: Northwestern University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Klebsiella pneumoniae has been classified into two types, classical K. pneumoniae (cKP) and hypervirulent K. pneumoniae (hvKP). cKP isolates are highly diverse and important causes of nosocomial infections; they include globally disseminated antibiotic-resistant clones. hvKP isolates are sensitive to most antibiotics but are highly virulent, causing community-acquired infections in healthy individuals. The virulence phenotype of hvKP is associated with pathogenicity loci responsible for siderophore and hypermucoid capsule production. Recently, convergent strains of K. pneumoniae, which possess features of both cKP and hvKP, have emerged and are cause of much concern. Here, we screen the genomes of 2,608 multidrug-resistant K. pneumoniae isolates from the United States and identify 47 convergent isolates. We perform phenotypic and genomic characterization of 12 representative isolates. These 12 convergent isolates contain a variety of antimicrobial resistance plasmids and virulence plasmids. Most convergent isolates contain aerobactin biosynthesis genes and produce more siderophores than cKP isolates but not more capsule. Unexpectedly, only 1 of the 12 tested convergent isolates has a level of virulence consistent with hvKP isolates in a murine pneumonia model. These findings suggest that additional studies should be performed to clarify whether convergent strains are indeed more virulent than cKP in mouse and human infections.

Date: 2023
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DOI: 10.1038/s41467-023-43802-1

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