title: Identification of SagA as a novel vaccine target for the prevention of Enterococcus faecium infections.
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.
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: A
authors: A
authors: Kropec
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: I G
authors: IG
authors: Sava
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: C
authors: C
authors: Vonend
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: T
authors: T
authors: Sakinc
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: E
authors: E
authors: Grohmann
authors: Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.
authors: J
authors: J
authors: Huebner
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D016470:Bacteremia / Q000517:prevention & control*; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001769:Blood / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D016984:Enterococcus faecium / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015870:Gene Expression; D016908:Gram-Positive Bacterial Infections / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009895:Opsonin Proteins / Q000097:blood; D010587:Phagocytosis / Q000276:immunology; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D009895:Opsonin Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic