Mutational analysis of glucose transport regulation and glucose-mediated virulence gene repression in Listeria monocytogenes

Mol Microbiol. 2011 Jul;81(1):274-93. doi: 10.1111/j.1365-2958.2011.07692.x. Epub 2011 May 25.

Abstract

Listeria monocytogenes transports glucose/mannose via non-PTS permeases and phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTS). Two mannose class PTS are encoded by the constitutively expressed mpoABCD and the inducible manLMN operons. The man operon encodes the main glucose transporter because manL or manM deletion significantly slows glucose utilization, whereas mpoA deletion has no effect. The PTS(Mpo) mainly functions as a constitutively synthesized glucose sensor controlling man operon expression by phosphorylating and interacting with ManR, a LevR-like transcription activator. EIIB(Mpo) plays a dual role in ManR regulation: P~EIIB(Mpo) prevailing in the absence of glucose phosphorylates and thereby inhibits ManR activity, whereas unphosphorylated EIIB(Mpo) prevailing during glucose uptake is needed to render ManR active. In contrast to mpoA, deletion of mpoB therefore strongly inhibits man operon expression and glucose consumption. A ΔptsI (EI) mutant consumes glucose at an even slower rate probably via GlcU-like non-PTS transporters. Interestingly, deletion of ptsI, manL, manM or mpoB causes elevated PrfA-mediated virulence gene expression. The PTS(Man) is the major player in glucose-mediated PrfA inhibition because the ΔmpoA mutant showed normal PrfA activity. The four mutants showing PrfA derepression contain no or only little unphosphorylated EIIAB(Man) (ManL), which probably plays a central role in glucose-mediated PrfA regulation.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gene Deletion
  • Gene Expression Regulation, Bacterial*
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / metabolism*
  • Listeria monocytogenes / genetics*
  • Listeria monocytogenes / growth & development
  • Listeria monocytogenes / pathogenicity*
  • Mannose / metabolism
  • Metabolic Networks and Pathways
  • Models, Biological
  • Peptide Termination Factors / genetics
  • Peptide Termination Factors / metabolism*
  • Virulence
  • Virulence Factors / genetics
  • Virulence Factors / metabolism*

Substances

  • Bacterial Proteins
  • Glucose Transport Proteins, Facilitative
  • Peptide Termination Factors
  • PrfA protein, Listeria monocytogenes
  • Virulence Factors
  • Glucose
  • Mannose