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Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella

View ORCID ProfileSebastian Bruchmann, View ORCID ProfileTheresa Feltwell, View ORCID ProfileJulian Parkhill, View ORCID ProfileFrancesca L. Short
doi: https://doi.org/10.1101/2020.10.30.362657
Sebastian Bruchmann
aDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
bWellcome Sanger Institute, Hinxton, United Kingdom
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Theresa Feltwell
bWellcome Sanger Institute, Hinxton, United Kingdom
cDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom
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Julian Parkhill
aDepartment of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
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Francesca L. Short
bWellcome Sanger Institute, Hinxton, United Kingdom
cDepartment of Medicine, University of Cambridge, Cambridge, United Kingdom
dDepartment of Molecular Sciences, Macquarie University, Sydney, Australia
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  • For correspondence: francesca.short@cantab.net francesca.short@mq.edu.au
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Abstract

Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pneumoniae pathogenesis is hampered by the fact that murine models of infection offer limited resolution for the non-hypervirulent strains which cause the majority of infections. We have performed genome-scale fitness profiling of a multidrug-resistant K. pneumoniae ST258 strain during infection of the insect Galleria mellonella, with the aim to determine if this model is suitable for large-scale virulence factor discovery in this pathogen. Our results demonstrated a dominant role for surface polysaccharides in infection, with contributions from siderophores, cell envelope proteins, purine biosynthesis genes and additional genes of unknown function. Comparison with a hypervirulent strain, ATCC 43816, revealed substantial overlap in important infection-related genes, as well as additional putative virulence factors that may be specific to ST258. Our analysis also identified a role for the metalloregulatory protein NfeR (also called YqjI) in virulence. Overall, this study offers new insight into the infection fitness landscape of K. pneumoniae ST258, and provides a framework for using the highly flexible, scalable G. mellonella infection model to dissect the molecular virulence mechanisms of K. pneumoniae and other bacterial pathogens.

Competing Interest Statement

The authors have declared no competing interest.

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Posted October 31, 2020.
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Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella
Sebastian Bruchmann, Theresa Feltwell, Julian Parkhill, Francesca L. Short
bioRxiv 2020.10.30.362657; doi: https://doi.org/10.1101/2020.10.30.362657
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Identifying virulence determinants of multidrug-resistant Klebsiella pneumoniae in Galleria mellonella
Sebastian Bruchmann, Theresa Feltwell, Julian Parkhill, Francesca L. Short
bioRxiv 2020.10.30.362657; doi: https://doi.org/10.1101/2020.10.30.362657

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