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The low-fidelity DNA Pol IV accelerates evolution of pathogenicity genes in Pseudomonas aeruginosa

Sofía D Castell1,2, Consuelo M Fernandez1, Ignacio N Tumas1

  • 1Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Departamento de Química Biológica Ranwel Caputto, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

Communications Biology
|August 2, 2025
PubMed

Insights

DNA polymerase IV (Pol IV) drives genomic instability in Pseudomonas aeruginosa by introducing mutations, particularly A-to-C changes. This enzyme

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Specialized DNA polymerases are crucial for cellular functions.
  • The mutagenic impact of error-prone polymerases on genomes remains incompletely understood.

Purpose of the Study:

  • To investigate the role of DNA polymerase IV (Pol IV) in genomic instability in Pseudomonas aeruginosa.
  • To elucidate the specific mutagenic mechanisms employed by Pol IV.

Main Methods:

  • Analysis of mutational signatures in Pseudomonas aeruginosa.
  • Investigation of nucleotide misincorporation by Pol IV.
  • Genomic location analysis of Pol IV-targeted genes.

Main Results:

  • Pol IV promotes genomic instability by misincorporating oxidized guanine nucleotides.
  • A distinct mutational signature of A-to-C transversions at AT sites (flanked by G/C) was identified.
  • Pol IV preferentially targeted pathogenicity genes near replication termination and rRNA operons, impairing gene function in 50% of events.

Conclusions:

  • Pol IV is a significant driver of genomic instability and mutation in P. aeruginosa.
  • The specific mutational patterns and gene targeting by Pol IV contribute to pathogen adaptation and diversification.
  • Pol IV-associated mutation signatures are present in clinical isolates, confirming its role in bacterial evolution.

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