Fine-tuning cellular levels of DprA ensures transformant fitness in the human pathogen Streptococcus pneumoniae

Mol Microbiol. 2018 Sep;109(5):663-675. doi: 10.1111/mmi.14068. Epub 2018 Jul 31.


Natural genetic transformation is a widespread mechanism of horizontal gene transfer. It involves the internalization of exogenous DNA as single strands and chromosomal integration via homologous recombination, promoting acquisition of new genetic traits. Transformation occurs during a distinct physiological state called competence. In Streptococcus pneumoniae, competence is controlled by ComDE, a two-component system induced by an exported peptide pheromone. DprA is universal among transformable species, strongly induced during pneumococcal competence, and crucial for pneumococcal transformation. Pneumococcal DprA plays three crucial roles in transformation and competence. Firstly, DprA protects internalized DNA from degradation. Secondly, DprA loads the homologous recombinase RecA onto transforming DNA to promote transformation. Finally, DprA interacts with the response regulator ComE to shut-off competence. Here, we explored the effect of altering the cellular levels of DprA on these three roles. High cellular levels of DprA were not required for the primary role of DprA as a transformation-dedicated recombinase loader or for protection of transforming DNA. In contrast, full expression of dprA was required for optimal competence shut-off and transformant fitness. High cellular levels of DprA thus ensure the fitness of pneumococcal transformants by mediating competence shut-off. This promotes survival and propagation of transformants, maximizing pneumococcal adaptive potential.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • DNA Primers / genetics
  • DNA Primers / metabolism
  • DNA Transformation Competence / drug effects
  • DNA Transformation Competence / physiology*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • Homologous Recombination
  • Humans
  • Isopropyl Thiogalactoside / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Rec A Recombinases / genetics
  • Rec A Recombinases / metabolism
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / pathogenicity*
  • Streptococcus pneumoniae / physiology*
  • Transformation, Bacterial / drug effects
  • Transformation, Bacterial / physiology*


  • Bacterial Proteins
  • ComE protein, Streptococcus pneumoniae
  • DNA Primers
  • DNA, Single-Stranded
  • DprA protein, bacteria
  • Membrane Proteins
  • Isopropyl Thiogalactoside
  • Rec A Recombinases