Expression of Staphylococcus epidermidis SdrG increases following exposure to an in vivo environment.
SdrG is a surface-associated fibrinogen binding protein present in most strains of Staphylococcus epidermidis. Surface expression of SdrG was not detected by flow cytometry or immunofluorescence microscopy on S. epidermidis 0-47 grown in nutrient broth or in the presence of human serum. sdrG transcript levels increased 1 hour following a shift from growth in nutrient broth to growth in the bloodstream of a mouse and resulted in a concomitant increase in protein levels as detected by immunofluorescence microscopy. The environmental signal(s) resulting in the increase in expression is elusive, as growth under conditions known to mimic in vivo conditions (elevated CO(2), iron limitation, human serum, and citrated human blood) did not affect expression of SdrG. Immunizing mice with either the N1N2N3 (amino acids 50 to 597) or N2N3 (amino acids 273 to 597) subdomain of the N-terminal A domain of recombinant SdrG (rSdrG) elicited a robust antibody response; however, only mice vaccinated with rSdrG(N23) exhibited a significant reduction in 0-47 recovered after experimental infection. Since SdrG is expressed early during infection in response to specific host environmental cues present in the bloodstream and since antibodies to it are effective in reducing bacteremia, SdrG possesses attributes of a vaccine component effective against the pathogenic form of the ubiquitous human commensal S. epidermidis.
Sellman
Bret R
BR
Wyeth Vaccine Research, 401 N. Middletown Rd., Pearl River, NY 10965, USA.
Timofeyeva
Yekaterina
Y
Nanra
Jasdeep
J
Scott
Adrienne
A
Fulginiti
James P
JP
Matsuka
Yury V
YV
Baker
Steve M
SM
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001769:Blood / Q000382:microbiology*; D002352:Carrier Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003470:Culture Media; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D016106:Methicillin Resistance; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014611:Vaccination
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; C112556:Fbe protein, bacteria; D011994:Recombinant Proteins