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 van Duin; Liang Chen; Barry N. Kreiswirth; S. Wesley Long; James M. Musser; Zackery P. Bulman; Richard G. Wunderink; Alan R. Hauser

doi:10.1038/s41467-023-43802-1

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 van Duin, Liang Chen, Barry N. Kreiswirth, S. Wesley Long, James M. Musser, Zackery P. BulmanRichard G. Wunderink, Alan R. Hauser

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Article number	7962
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-43802-1
State	Published - Dec 2023

Funding

This work was funded by American Heart Association grant 837089 (T.K.), Chicago Biomedical Consortium Catalyst Award (A.H., Z.B.), and National Institute of Health grants T32 AI007476 (T.K.), R01 AI118257 (A.H.), R21 AI153953 (A.H.), K24 AI104831 (A.H.), R21 AI164254 (A.H.), U19 AI35964 (A.H.), T32 AI095207 (R.M., A.H.), R01 AI173064 (Z.P.B., A.H., E.O.) The funding sources had no influence on the design of the study and collection, analysis, interpretation of data, or writing of the manuscript.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-023-43802-1

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Kochan, T. J., Nozick, S. H., Valdes, A., Mitra, S. D., Cheung, B. H., Lebrun-Corbin, M., Medernach, R. L., Vessely, M. B., Mills, J. O., Axline, C. M. R., Nelson, J. A., VanGosen, E. M., Ward, T. J., Ozer, E. A., van Duin, D., Chen, L., Kreiswirth, B. N., Long, S. W., Musser, J. M., ... Hauser, A. R. (2023). Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence. Nature communications, 14(1), Article 7962. https://doi.org/10.1038/s41467-023-43802-1

@article{a679db39af06406e8993c7709c368981,

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

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.",

author = "Kochan, {Travis J.} and Nozick, {Sophia H.} and Aliki Valdes and Mitra, {Sumitra D.} and Cheung, {Bettina H.} and Marine Lebrun-Corbin and Medernach, {Rachel L.} and Vessely, {Madeleine B.} and Mills, {Jori O.} and Axline, {Christopher M.R.} and Nelson, {Julia A.} and VanGosen, {Ethan M.} and Ward, {Timothy J.} and Ozer, {Egon A.} and {van Duin}, David and Liang Chen and Kreiswirth, {Barry N.} and Long, {S. Wesley} and Musser, {James M.} and Bulman, {Zackery P.} and Wunderink, {Richard G.} and Hauser, {Alan R.}",

note = "Publisher Copyright: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",

year = "2023",

month = dec,

doi = "10.1038/s41467-023-43802-1",

language = "English (US)",

volume = "14",

journal = "Nature communications",

issn = "2041-1723",

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Kochan, TJ, Nozick, SH, Valdes, A, Mitra, SD, Cheung, BH, Lebrun-Corbin, M, Medernach, RL, Vessely, MB, Mills, JO, Axline, CMR, Nelson, JA, VanGosen, EM, Ward, TJ, Ozer, EA, van Duin, D, Chen, L, Kreiswirth, BN, Long, SW, Musser, JM, Bulman, ZP, Wunderink, RG & Hauser, AR 2023, 'Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence', Nature communications, vol. 14, no. 1, 7962. https://doi.org/10.1038/s41467-023-43802-1

TY - JOUR

T1 - Klebsiella pneumoniae clinical isolates with features of both multidrug-resistance and hypervirulence have unexpectedly low virulence

AU - Kochan, Travis J.

AU - Nozick, Sophia H.

AU - Valdes, Aliki

AU - Mitra, Sumitra D.

AU - Cheung, Bettina H.

AU - Lebrun-Corbin, Marine

AU - Medernach, Rachel L.

AU - Vessely, Madeleine B.

AU - Mills, Jori O.

AU - Axline, Christopher M.R.

AU - Nelson, Julia A.

AU - VanGosen, Ethan M.

AU - Ward, Timothy J.

AU - Ozer, Egon A.

AU - van Duin, David

AU - Chen, Liang

AU - Kreiswirth, Barry N.

AU - Long, S. Wesley

AU - Musser, James M.

AU - Bulman, Zackery P.

AU - Wunderink, Richard G.

AU - Hauser, Alan R.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

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

Abstract

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