Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci

Abstract

Strains of type III group B streptococci isolated from patients with neonatal sepsis are generally resistant to complement-mediated phagocytic killing in the absence of specific antibody. It has been suggested that the resistance of type HI group B streptococci to phagocytosis results from inhibition of alternative-complementpathway activation by sialic acid residues of the type III polysaccharide. To better define the relationship between structural features of the type III capsule and resistance of type III group B streptococci to complement-mediated phagocytic killing, we measured deposition of human C3 on group B streptococcal strains with altered capsule phenotypes. C3 binding was quantified by incubating bacteria with purified human 12511C3 in 10% senrm. Wild-type group B Streptococcus sp. strain COH1 bound eightfold fewer C3 molecules than did either of two isogenic mutant strains, one expressing a sialic acid-deficient capsule and the other lacking capsule completely. Similar results were obtained when the incubation with 12-I-C3 was performed in serum chelated with Mg-ethylene glycol-bis(3-aminoethyl ether)-N,NN',N'-tetraacetic acid (MgEGTA), suggesting that the majority of C3 deposition occurred via the alternative pathway. In contrast to the wild-type strain, which was relatively resistant, both mutant strains were killed by human leukocytes in 10%/1 serum with or without MgEGTA. We also measured C3 binding to 14 wild-type strains of type IH group B streptococci expressing various amounts of capsule. Comparison of degree of encapsulation with C3 binding revealed a significant inverse correlation (r = -0.72; P < 0.01). C3 fagments released by methylamine treatment of wild-type strain COH1 were predominantly in the form of C3bi, while those released from the acapsular mutant were predominantly C3b and those from the asialo mutant represented approximately equal amounts of C3b and C3bi. We conclude from these studies that the sialylated type III capsular polysaccharide inhibits alternative-pathway activation, prevents C3 deposition on group B streptococci, and protects the organisms from phagocytic killing.

Acquisition of factor H by a novel surface protein on group BStreptococcuspromotes complement degradation

“…ii) Amounts of C3, C5, and C9 in Wt GBS and acapsular GBS (AcapGBS) were estimated by densitometry and plotted in comparison to complement components formed in E. coli. type, as reported earlier (6). However, ϳ50 -60% more of C3c and C3d could also be observed over time on the mutant strain, as shown by densitometric analysis of the C3d band with respect to the ␤ band (taken as a measure of total complement) ( Fig.…”

“…GBS is known to activate the third component of complement through the alternative pathway in which FH acts as a cofactor to FI in degrading C3b (5,6,7). These studies suggested that deposition of complement C3b on Wt GBS was regulated by the capsule, leading to a hypothesis that the capsule binds FH to break down or inactivate C3b into various smaller chains, such as C3c (iC3b) and C3d.…”

“…In the absence of capsule-specific antibodies, C3 interacts with bacterial surface components, leading to the activation of the alternative complement pathway. The amount and form of C3 (C3b and its inactive cleaved product, iC3b) deposited on the surface of GBS has been correlated with its survival in the host (6,7). Marques et al (6) demonstrated that wild-type GBS (Wt GBS) binds lower levels of active C3b as compared to the capsule mutants and postulated that the lower levels could be due to the binding of factor H (FH) by sialic acid, as has been demonstrated for other microbes, such as Neisseria gonorrhoeae (6,8).…”

Streptococcus suis and group B Streptococcus differ in their interactions with murine macrophages

“…On the other hand, no di¡erences were observed between this strain and its unencapsulated mutant, which indicates that the capsule is not necessarily an antiphagocytic factor for this bacterial species. Controversially, previous reports have assumed an antiphagocytic role of GBS type III capsule since encapsulated bacteria were resistant to opsonophagocytic killing by PMN in the absence of speci¢c antibodies, while unencapsulated or asialo mutants were susceptible [11,12,26]. However, in these studies, the techniques used allowed the study of bacterial killing rather than phagocytosis, since no di¡erentiation of intracellular and extracellular bacteria was done.…”

Sialic acid and biology of life: An introduction

“…The PSA capsule of N. meningitides serogroup B and E. coli K1 is poorly immunogenic and PSA reveal structural similarities to mammalian neuronal cell adhesion molecule, NCAM [160]. The sialylated capsule of S. agalactiae inhibits phagocytosis, impairs C3 deposition on the cell surface, and prevents complement alternative pathway [161] activation. LPS sialylation inhibits the complement alternative pathway in both N. gonorrhoeae and non-typable H. influenza (NTHi) [162,163].…”