Identification of SagA as a novel vaccine target for the prevention of Enterococcus faecium infections

Microbiology (Reading). 2011 Dec;157(Pt 12):3429-3434. doi: 10.1099/mic.0.053207-0. Epub 2011 Sep 8.

Abstract

Infections caused by multiresistant Gram-positive bacteria represent a major health burden in the community as well as in hospitalized patients. Enterococci, especially Enterococcus faecium, are well-known pathogens of hospitalized patients and are frequently linked with resistance against multiple antibiotics, which compromises effective therapy. Rabbit immune serum raised against heat-killed E. faecium E155, a HiRECC clone, was used in an opsonophagocytic assay, an inhibition assay and a mouse bacteraemia model to identify targets of opsonic and protective antibodies. Serum against whole heat-killed bacteria was opsonic and recognized a protein of about 72 kDa that was abundantly secreted. This protein, identified as SagA by LC-ES-MS/MS, was expressed in Escherichia coli and purified. Rabbit serum raised against the purified protein showed opsonic killing activity that was inhibited by almost 100% using 100 µg purified protein ml(-1). In a mouse bacteraemia model, a statistically significant reduction of the colony counts in blood was shown with immune rabbit serum compared with preimmune serum using the homologous and a heterologous vancomycin-resistant enterococci (VRE) strain. These results indicate that SagA could be used as a promising vaccine target to treat and/or prevent VRE bacteraemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacteremia / prevention & control*
  • Bacterial Load
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • Blood / immunology
  • Blood / microbiology
  • Disease Models, Animal
  • Enterococcus faecium / genetics
  • Enterococcus faecium / immunology*
  • Escherichia coli / genetics
  • Female
  • Gene Expression
  • Gram-Positive Bacterial Infections / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Opsonin Proteins / blood
  • Phagocytosis / immunology
  • Rabbits
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Vaccines
  • Opsonin Proteins
  • Recombinant Proteins
  • Vaccines, Synthetic