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Genetic determinants of pOXA-48 plasmid maintenance and propagation in Escherichia coli

Yannick Baffert1, Nathan Fraikin1, Yasmine Makhloufi1

  • 1Microbiologie Moléculaire et Biochimie Structurale (MMSB), Université Lyon 1, CNRS, Inserm, UMR5086, Lyon, France.

Nature Communications
|August 19, 2025
PubMed

Insights

Researchers identified key genetic factors enabling the spread of pOXA-48 plasmids, which drive antibiotic resistance. This includes a new toxin-antitoxin system and essential maintenance factors, crucial for understanding multidrug resistance.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Conjugative plasmids, like pOXA-48, are major contributors to antibiotic resistance spread.
  • pOXA-48 plasmids (IncL group) are primary carriers of carbapenem resistance in Enterobacteriaceae.
  • Limited understanding exists regarding the propagation mechanisms of pOXA-48 plasmids.

Purpose of the Study:

  • To identify genetic elements essential for pOXA-48 plasmid stability, replication, and transfer.
  • To elucidate the molecular mechanisms behind the successful spread of carbapenem resistance.

Main Methods:

  • Transposon sequencing (Tn-seq) was employed to screen for essential genes.
  • Genetic analysis focused on plasmid maintenance, replication, and conjugation machinery.

Main Results:

  • A novel type I toxin-antitoxin system was identified.
  • Uncharacterized essential maintenance factors for plasmid stability were discovered.
  • Key components of the type IV secretion system and regulatory elements for conjugation were characterized.

Conclusions:

  • This study reveals critical genetic factors governing pOXA-48 plasmid biology.
  • Insights into plasmid maintenance and spread mechanisms are provided, advancing understanding of multidrug resistance dissemination.

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