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Cited by 12Antibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyEscherichia coli research studies

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Transposon mutagenesis screen in Klebsiella pneumoniae identifies genetic determinants required for growth in human urine and serum

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Gray, Jessica, Torres, Von Vergel L, Goodall, Emily, McKeand, Samantha A, Scales, Danielle, Collins, Christy, Wetherall, Laura, Lian, Zheng Jie, Bryant, Jack A, Milner, Matthew T, Dunne, Karl A, Icke, Christopher, Rooke, Jessica L, Schneiders, Thamarai, Lund, Peter A, Cunningham, Adam F, Cole, Jeff A, Henderson, Ian R·2024·eLife
DOI 10.7554/elife.88971.3PMC PMC11349299

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Abstract

Klebsiella pneumoniae is a global public health concern due to the rising myriad of hypervirulent and multidrug-resistant clones both alarmingly associated with high mortality. The molecular mechanisms underpinning these recalcitrant K. pneumoniae infection, and how virulence is coupled with the emergence of lineages resistant to nearly all present-day clinically important antimicrobials, are unclear. In this study, we performed a genome-wide screen in K. pneumoniae ECL8, a member of the endemic K2-ST375 pathotype most often reported in Asia, to define genes essential for growth in a nutrient-rich laboratory medium (Luria-Bertani [LB] medium), human urine, and serum. Through transposon directed insertion-site sequencing (TraDIS), a total of 427 genes were identified as essential for growth on LB agar, whereas transposon insertions in 11 and 144 genes decreased fitness for growth in either urine or serum, respectively. These studies not only provide further knowledge on the genetics of this pathogen but also provide a strong impetus for discovering new antimicrobial targets to improve current therapeutic options for K. pneumoniae infections.

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Metadata

Authors
Gray, J., Torres, V. V. L., Goodall, E., McKeand, S. A., Scales, D., Collins, C., Wetherall, L., Lian, Z. J., Bryant, J. A., Milner, M. T., Dunne, K. A., Icke, C., Rooke, J. L., Schneiders, T., Lund, P. A., Cunningham, A. F., Cole, J. A., & Henderson, I. R.
Affiliations
  • The University of Queensland (AU)
  • University of Birmingham (GB)
  • Institute of Microbiology and Infection, University of Birmingham
Corresponding author
Henderson, Ian R
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2024-08-27
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.88971.3
PMC
PMC11349299
OpenAlex
W4382678902
Cited by
12
References
2
Citations by year
2026: 6 · 2025: 4 · 2024: 2
FWCI
1.02
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
Biotechnology and Biological Sciences Research Council (MIBTP)
Topics
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Keywords
Klebsiella pneumoniae, transposon mutagenesis screen, essential genes, human urine, serum, virulence, multidrug resistance, antimicrobial drug targets, TraDIS
MeSH terms
DNA Transposable Elements, Humans, Klebsiella Infections, Klebsiella pneumoniae, Urine, Mutagenesis, Insertional, Mutagenesis, Serum

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