Expression of Staphylococcus epidermidis SdrG increases following exposure to an in vivo environment

Wyeth Vaccine Research, Pearl River, NY

^* To whom correspondence should be addressed. Email: timofey{at}wyeth.com.

	Abstract

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 immunofluorescent microscopy on S. epidermidis 0-47 grown in nutrient broth or in the presence of human serum. Transcript levels of sdrG increased one hour following a shift from growth in nutrient broth to the bloodstream of a mouse and resulted in a concomitant increase in protein levels as detected by immunofluorescent microscopy. The environmental signal(s) resulting in the increase in expression are elusive, as growth in conditions known to mimic in vivo conditions (elevated CO₂, iron limitation, human serum and citrated human blood) did not affect expression of SdrG. Immunizing mice with either the N1N2N3 (amino acids 50-597) or N2N3 (amino acids 273-597) subdomains of the N-terminal A domain of 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.