Sensitivity to the two-peptide bacteriocin lactococcin G is dependent on UppP, an enzyme involved in cell-wall synthesis

Mol Microbiol. 2014 Jun;92(6):1177-87. doi: 10.1111/mmi.12632. Epub 2014 May 23.


Most bacterially produced antimicrobial peptides (bacteriocins) are thought to kill target cells by a receptor-mediated mechanism. However, for most bacteriocins the receptor is unknown. For instance, no target receptor has been identified for the two-peptide bacteriocins (class IIb), whose activity requires the combined action of two individual peptides. To identify the receptor for the class IIb bacteriocin lactococcin G, which targets strains of Lactococcus lactis, we generated 12 lactococcin G-resistant mutants and performed whole-genome sequencing to identify mutations causing the resistant phenotype. Remarkably, all had a mutation in or near the gene uppP (bacA), encoding an undecaprenyl pyrophosphate phosphatase; a membrane protein involved in peptidoglycan synthesis. Nine mutants had stop codons or frameshifts in the uppP gene, two had point mutations in putative regulatory regions and one caused an amino acid substitution in UppP. To verify the receptor function of UppP, it was shown that growth of non-sensitive Streptococcus pneumoniae could be inhibited by lactococcin G when L. lactis uppP was expressed in this bacterium. Furthermore, we show that the related class IIb bacteriocin enterocin 1071 also uses UppP as receptor. The approach used here should be broadly applicable to identify receptors for other bacteriocins as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteriocins / pharmacology*
  • Cell Wall / metabolism*
  • DNA Mutational Analysis
  • Drug Resistance, Bacterial
  • Genome, Bacterial
  • Lactococcus lactis / drug effects*
  • Lactococcus lactis / enzymology*
  • Lactococcus lactis / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Peptidoglycan / metabolism*
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism*
  • Sequence Analysis, DNA
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / genetics


  • Anti-Bacterial Agents
  • Bacteriocins
  • Membrane Proteins
  • Peptidoglycan
  • lactococcin G
  • Pyrophosphatases
  • undecaprenyl pyrophosphate phosphatase