Environmental and genetic regulation of Streptococcus pneumoniae galactose catabolic pathways

Nat Commun. 2024 Jun 17;15(1):5171. doi: 10.1038/s41467-024-49619-w.

Abstract

Efficient utilization of nutrients is crucial for microbial survival and virulence. The same nutrient may be utilized by multiple catabolic pathways, indicating that the physical and chemical environments for induction as well as their functional roles may differ. Here, we study the tagatose and Leloir pathways for galactose catabolism of the human pathogen Streptococcus pneumoniae. We show that galactose utilization potentiates pneumococcal virulence, the induction of galactose catabolic pathways is influenced differentially by the concentration of galactose and temperature, and sialic acid downregulates galactose catabolism. Furthermore, the genetic regulation and in vivo induction of each pathway differ, and both galactose catabolic pathways can be turned off with a galactose analogue in a substrate-specific manner, indicating that galactose catabolic pathways can be potential drug targets.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Female
  • Galactose* / metabolism
  • Gene Expression Regulation, Bacterial*
  • Hexoses / metabolism
  • Humans
  • Metabolic Networks and Pathways / genetics
  • Mice
  • N-Acetylneuraminic Acid / metabolism
  • Pneumococcal Infections / metabolism
  • Pneumococcal Infections / microbiology
  • Streptococcus pneumoniae* / genetics
  • Streptococcus pneumoniae* / metabolism
  • Temperature
  • Virulence / genetics

Substances

  • Galactose
  • Hexoses
  • tagatose
  • N-Acetylneuraminic Acid
  • Bacterial Proteins