IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge.
Staphylococcus aureus is the most frequent cause of bacteremia and hospital-acquired infection, however a vaccine that prevents staphylococcal disease is currently not available. Two sortase-anchored surface proteins, IsdA and IsdB, have been identified as subunit vaccines that, following active immunization, protect experimental animals against intravenous challenge with staphylococci. Here we investigate the molecular basis of this immunity and report that, when passively transferred to naïve mice, purified antibodies directed against IsdA or IsdB protected against staphylococcal abscess formation and lethal intravenous challenge. When added to mouse blood, IsdA- or IsdB-specific antibodies did not promote rapid opsonophagocytic killing of wild-type staphylococci. Antibodies directed against IsdA interfered with heme-binding and IsdB antibodies perturbed the ability of this surface protein to bind hemoglobin. As the structural genes for isdA and isdB are required for heme-iron scavenging during the pathogenesis of infection, we hypothesize that IsdA and IsdB antibodies may at least in part provide protection against staphylococci by interfering with the pathogen's heme-iron scavenging mechanisms.
Department of Microbiology, University of Chicago, 920 East 58th Street, Chicago, IL, USA.
Hwan Keun
HK
Kim
Andrea
A
DeDent
Alice G
AG
Cheng
Molly
M
McAdow
Fabio
F
Bagnoli
Dominique M
DM
Missiakas
Olaf
O
Schneewind
D000038:Abscess / Q000276:immunology / Q000382:microbiology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D027682:Cation Transport Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D005260:Female; D006418:Heme / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007116:Immunization, Passive; D007668:Kidney / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011817:Rabbits; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D027682:Cation Transport Proteins; D006454:Hemoglobins; C512791:IsdA protein, Staphylococcus aureus; C510010:IsdB protein, Staphylococcus aureus; D006418:Heme