Characterization of a novel fucose-regulated promoter (PfcsK) suitable for gene essentiality and antibacterial mode-of-action studies in Streptococcus pneumoniae

J Bacteriol. 2003 Mar;185(6):2051-8. doi: 10.1128/JB.185.6.2051-2058.2003.

Abstract

The promoter of the Streptococcus pneumoniae putative fuculose kinase gene (fcsK), the first gene of a novel fucose utilization operon, is induced by fucose and repressed by glucose or sucrose. When the streptococcal polypeptide deformylase (PDF) gene (def1, encoding PDF) was placed under the control of P(fcsK), fucose-dependent growth of the S. pneumoniae (P(fcsK)::def1) strain was observed, confirming the essential nature of PDF in this organism. The mode of antibacterial action of actinonin, a known PDF inhibitor, was also confirmed with this strain. The endogenous fuculose kinase promoter is a tightly regulated, titratable promoter which will be useful for target validation and for confirmation of the mode of action of novel antibacterial drugs in S. pneumoniae.

Publication types

  • Evaluation Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amidohydrolases*
  • Aminopeptidases / antagonists & inhibitors
  • Aminopeptidases / genetics
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Enzyme Inhibitors / pharmacology
  • Fucose / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Genes, Essential*
  • Humans
  • Hydroxamic Acids / pharmacology
  • Molecular Sequence Data
  • Operon
  • Promoter Regions, Genetic / genetics*
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pneumoniae / genetics
  • Streptococcus pneumoniae / growth & development
  • Streptococcus pneumoniae / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Fucose
  • Aminopeptidases
  • Amidohydrolases
  • peptide deformylase
  • actinonin