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Point mutations in functionally diverse genes are associated with increased natural DNA transformation in multidrug

Flora Peillard-Fiorente1, Nguyen Phuong Pham1, Hélène Gingras1

  • 1Centre de Recherche en Infectiologie, Axe des Maladies Infectieuses et Immunitaires du CHU de Québec and Département de Microbiologie, Infectiologie et Immunologie, Faculté de Médecine, Université Laval, 2707 Bd Laurier, Québec, QC G1V 4G2, Canada.

Nucleic Acids Research
|December 14, 2024
PubMed

Insights

Streptococcus pneumoniae can naturally transform DNA without external signals, enhancing adaptation and multidrug resistance. Genetic mutations identified increase this natural transformation ability, crucial for bacterial evolution.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • DNA transformation drives Streptococcus pneumoniae adaptation and multidrug resistance (MDR).
  • Artificial competence stimulating peptide (CSP) typically triggers laboratory transformation.
  • Exogenous CSP is sometimes unnecessary for transformation, depending on strain and media.

Purpose of the Study:

  • To identify Streptococcus pneumoniae mutants with enhanced natural transformation capabilities in standard media.
  • To investigate genetic factors influencing natural transformation independent of exogenous CSP.
  • To correlate mutations enhancing transformation with those linked to multidrug resistance.

Main Methods:

  • Chemogenomic screening using chemical mutagenesis to select for hyper-transformable mutants.
  • Genome-wide sequencing of selected mutants to identify genetic mutations.
  • Genome-wide association studies comparing multidrug-resistant and sensitive clinical isolates.

Main Results:

  • Identified diverse gene mutations that significantly increase natural DNA transformation in Streptococcus pneumoniae.
  • Demonstrated that mutations enhancing transformation are prevalent and can occur naturally.
  • Found overlap between mutations increasing transformation and those associated with multidrug resistance in clinical isolates.

Conclusions:

  • Streptococcus pneumoniae possesses an inherent capacity for natural transformation, adaptable through genetic mutation.
  • Mutations facilitating DNA transformation are selected for by the bacterium, contributing to its lifestyle.
  • Understanding these mutations offers insights into bacterial adaptation and the emergence of antibiotic resistance.

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