PUBLICATION

Decoration of the enterococcal polysaccharide antigen EPA is essential for virulence, cell surface charge and interaction with effectors of the innate immune system

Authors
Smith, R.E., Salamaga, B., Szkuta, P., Hajdamowicz, N., Prajsnar, T.K., Bulmer, G.S., Fontaine, T., Kołodziejczyk, J., Herry, J.M., Hounslow, A.M., Williamson, M.P., Serror, P., Mesnage, S.
ID
ZDB-PUB-190507-22
Date
2019
Source
PLoS pathogens   15: e1007730 (Journal)
Registered Authors
Prajsnar, Thomasz
Keywords
none
MeSH Terms
  • Animals
  • Antigens, Surface/genetics
  • Antigens, Surface/immunology*
  • Antigens, Surface/metabolism
  • Antimicrobial Cationic Peptides/pharmacology
  • Bacterial Proteins/genetics
  • Bacterial Proteins/metabolism
  • Enterococcus faecalis/genetics
  • Enterococcus faecalis/immunology
  • Enterococcus faecalis/pathogenicity*
  • Gram-Positive Bacterial Infections/immunology*
  • Gram-Positive Bacterial Infections/metabolism
  • Gram-Positive Bacterial Infections/microbiology*
  • Muramidase/immunology*
  • Muramidase/metabolism
  • Mutagenesis
  • Mutation
  • Polysaccharides/immunology*
  • Polysaccharides/metabolism
  • Virulence*
  • Zebrafish/growth & development
  • Zebrafish/immunology
  • Zebrafish/microbiology
PubMed
31048927 Full text @ PLoS Pathog.
Abstract
Enterococcus faecalis is an opportunistic pathogen with an intrinsically high resistance to lysozyme, a key effector of the innate immune system. This high level of resistance requires a complex network of transcriptional regulators and several genes (oatA, pgdA, dltA and sigV) acting synergistically to inhibit both the enzymatic and cationic antimicrobial peptide activities of lysozyme. We sought to identify novel genes modulating E. faecalis resistance to lysozyme. Random transposon mutagenesis carried out in the quadruple oatA/pgdA/dltA/sigV mutant led to the identification of several independent insertions clustered on the chromosome. These mutations were located in a locus referred to as the enterococcal polysaccharide antigen (EPA) variable region located downstream of the highly conserved epaA-epaR genes proposed to encode a core synthetic machinery. The epa variable region was previously proposed to be responsible for EPA decorations, but the role of this locus remains largely unknown. Here, we show that EPA decoration contributes to resistance towards charged antimicrobials and underpins virulence in the zebrafish model of infection by conferring resistance to phagocytosis. Collectively, our results indicate that the production of the EPA rhamnopolysaccharide backbone is not sufficient to promote E. faecalis infections and reveal an essential role of the modification of this surface polymer for enterococcal pathogenesis.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping