Capsule production and growth phase influence binding of complement to Staphylococcus aureus.
Complement-mediated opsonization of bacteria by C3 binding is an important component of the host innate immune system. Little information is available concerning the interaction between complement proteins and capsule type 5 and 8 Staphylococcus aureus strains, even though these isolates are responsible for approximately 70% of human staphylococcal infections. To investigate the importance of an intact complement pathway in an experimental staphylococcal infection, control and C3-depleted mice were challenged intravenously with 10(7) CFU of a serotype 5 S. aureus isolate. Whereas only 8% of the control mice succumbed to the infection, 64% of the complemented-depleted animals died. In vitro parameters of C3 binding to two heavily encapsulated (CP++) strains, three encapsulated (CP+) strains, and an isogenic capsule-negative (CP-) mutant were examined. The alternative pathway contributed 90% of C3 binding in 20% serum at 30 min, whereas it accounted for only 13% of C3 binding in 2% serum. Stationary-phase organisms bound only 10% as much C3 as mid-log-phase organisms; this was only in part due to capsule. When the S. aureus strains were cultivated on solid medium, the CP++ isolates bound 50% less C3 than CP+ strains; a CP+ strain bound 42% less C3 than the CP- mutant. Both C3b and iC3b fragments of C3 bound to S. aureus cells, and about one-third of the bound C3 was shed from the staphylococcal surface as iC3b, regardless of the CP phenotype of the strain. Thus, the phase of growth and presence of capsule are critical to opsonization.
Cunnion
K M
KM
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA. Cunni003@mc.duke.edu
Lee
J C
JC
Frank
M M
MM
D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology; D000818:Animals; D016470:Bacteremia / Q000097:blood / Q000276:immunology / Q000382:microbiology; D016667:Bacterial Capsules / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology; D037222:Collectins; D003176:Complement C3 / Q000276:immunology*; D003179:Complement C3b / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism
D002352:Carrier Proteins; D037222:Collectins; D003176:Complement C3; D003179:Complement C3b