Deletion analysis of Streptococcus pneumoniae late competence genes distinguishes virulence determinants that are dependent or independent of competence induction

Mol Microbiol. 2015 Jul;97(1):151-65. doi: 10.1111/mmi.13016. Epub 2015 Apr 24.

Abstract

The competence regulon of Streptococcus pneumoniae (pneumococcus) is crucial for genetic transformation. During competence development, the alternative sigma factor ComX is activated, which in turn, initiates transcription of 80 'late' competence genes. Interestingly, only 16 late genes are essential for genetic transformation. We hypothesized that these late genes that are dispensable for competence are beneficial to pneumococcal fitness during infection. These late genes were systematically deleted, and the resulting mutants were examined for their fitness during mouse models of bacteremia and acute pneumonia. Among these, 14 late genes were important for fitness in mice. Significantly, deletion of some late genes attenuated pneumococcal fitness to the same level in both wild-type and ComX-null genetic backgrounds, suggesting that the constitutive baseline expression of these genes was important for bacterial fitness. In contrast, some mutants were attenuated only in the wild-type genetic background but not in the ComX-null background, suggesting that specific expression of these genes during competence state contributed to pneumococcal fitness. Increased virulence during competence state was partially caused by the induction of allolytic enzymes that enhanced pneumolysin release. These results distinguish the role of basal expression versus competence induction in virulence functions encoded by ComX-regulated late competence genes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteremia / microbiology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • DNA Transformation Competence / genetics*
  • Disease Models, Animal
  • Gene Deletion*
  • Gene Expression Regulation, Bacterial
  • Genetic Fitness
  • Mice
  • Mutation
  • Pneumococcal Infections / microbiology*
  • Pneumonia, Pneumococcal / microbiology
  • Regulon
  • Streptococcus pneumoniae / genetics*
  • Streptococcus pneumoniae / pathogenicity*
  • Streptolysins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virulence / genetics

Substances

  • Bacterial Proteins
  • ComX protein, Streptococcus
  • Streptolysins
  • Transcription Factors
  • plY protein, Streptococcus pneumoniae