STAPHYLOCOCCUS-AUREUS SEROTYPE-5 CAPSULAR POLYSACCHARIDE IS ANTIPHAGOCYTIC AND ENHANCES BACTERIAL VIRULENCE IN A MURINE BACTEREMIA MODEL

Controversy persists over the role that the capsular polysaccharide pl ays in the pathogenesis of Staphylococcus aureus infections. To addres s this issue, we compared the mouse virulence of S. aureus Reynolds an d capsule-defective mutant strains cultivated under conditions of high or low capsule expression. Strain Reynolds cells cultivated on Columb ia salt agar plates expressed similar to 100-fold more type 5 capsular polysaccharide than did cells cultivated in Columbia salt broth. The relative virulence of strain Reynolds and its capsule-defective mutant s after growth on either solid or liquid medium was examined in mice c hallenged intraperitoneally or intravenously. The results indicated th at agar-grown Reynolds cells were cleared from the bloodstream of mice less readily than broth-grown Reynolds cells. When the parental and m utant strains were cultivated on solid medium, strain Reynolds sustain ed a higher level of bacteremia than did the capsular mutants. We perf ormed in vitro opsonophagocytic killing assays to determine whether st aphylococcal virulence for mice correlated with resistance to phagocyt osis, S. aureus Reynolds cultivated on solid medium was susceptible to phagocytic killing only in the presence of specific capsular antibodi es and complement. Strain Reynolds grown in broth showed opsonic requi rements for phagocytic killing that were similar to those of the capsu lar mutants (grown in broth or on agar); i.e., the bacteria were opson ized for phagocytosis by nonimmune serum with complement activity. The se studies indicate that optimal expression of capsule enhances bacter ial virulence in the mouse model of bacteremia, probably by rendering the organisms resistant to opsonophagocytic killing by leukocytes.