Studies on the mechanism of bacterial resistance to complement-mediated killing. III. C5b-9 deposits stably on rough and type 7 S. pneumoniae without causing bacterial killing.
Gram-positive cocci resist direct killing by serum. The mechanism of resistance was studied by measuring consumption of terminal complement components from serum and uptake of purified, radiolabeled C7 and C9 on rough and encapsulated type 7 Streptococcus pneumoniae. Extensive consumption of C5, C7, and C9 occurred when 5 X 10(8) rough or type 7 pneumococci were incubated for 1 hr in 10% pooled normal human serum (PNHS). Approximately 10,000 molecules of C7 and C9 bound per organism during the same period of incubation. Twenty to 30% of C7 and C9 was released from rough organisms. Release was not due to autolysis since it occurred with glutaraldehyde-fixed organisms as well as in S. pneumoniae that were rendered resistant to autolysis by growth in ethanolamine. Between 10 and 30% of bound 125IC9 counts were eluted from the rough and type 7 organisms by incubation in 1 M NaCl or 0.01 M EDTA, which suggests that bound C5b-9 was not attached by predominantly ionic interactions. Elution of 44 to 74% of 125IC9 from live and glutaraldehyde-fixed organisms by 1% sodium deoxycholate suggests that hydrophobic bonds are involved in C5b-9 attachment. Trypsin cleaved 67 and 55% of 125IC9 counts from live rough and type 7 S. pneumoniae, respectively which indicates that the bound complex is not protected by the cell wall from proteolytic attack. Serum resistance in S. pneumoniae does not represent a failure to form C5b-9 on the bacterial cell wall but apparently reflects a failure of the bound complex to penetrate the thick peptidoglycan layer.
D001770:Blood Bactericidal Activity; D003182:Complement C5 / Q000378:metabolism; D003184:Complement C7 / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism
D003182:Complement C5; D003184:Complement C7; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins