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

AI Article Synopsis

  • Klebsiella pneumoniae infections are a significant public health concern, particularly due to the emergence of drug-resistant strains.
  • Traditional mouse models for studying the pathogenesis of these infections are limited, leading researchers to utilize Galleria mellonella larvae as an alternative model for large-scale studies.
  • Through genome-scale fitness profiling of a multidrug-resistant K. pneumoniae strain in G. mellonella, the study identified key virulence factors, including surface polysaccharides and other genes, while also highlighting the role of the metalloregulatory protein NfeR in infection.

Article 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 non-hypervirulent strains which cause the majority of infections. The insect Galleria mellonella larva is a widely used alternative model organism for bacterial pathogens. We have performed genome-scale fitness profiling of a multidrug-resistant K. pneumoniae ST258 strain during infection of G. mellonella, 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 specific to ST258, reflecting strain-dependent fitness effects. Our analysis also identified a role for the metalloregulatory protein NfeR (YqjI) in virulence. Overall, this study offers new insight into the infection fitness landscape of K. pneumoniae, and provides a framework for using the highly flexible and easily scalable G. mellonella infection model to dissect molecular virulence mechanisms of bacterial pathogens.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981267PMC
http://dx.doi.org/10.1093/femspd/ftab009DOI Listing

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