Antibody-independent Classical Pathway-mediated Opsonophagocytosis of Type Ia, Group B Streptococcus

Abstract

AB S T R A C T The opsonophagocytic requirements of human sera containing endogenous complement for a variety of type Ia, and group B streptococcal strains were defined. Significant reduction (290%) in colonyforming units was noted after a 40-min incubation for the highly encapsulated, mouse-passed prototype strain 090 by sera containing moderate to high concentrations of antibody to type Ia polysaccharide (mean, 16.5 gg/ml), whereas bacterial growth occurred in 25 sera with low levels of specific antibody (mean, 2.1 ug/ml). This absolute requirement for a critical amount of specific antibody in promoting opsonophagocytic killing of strain 090 was not found when 18 fresh clinical type la isolates were tested. In antibody-deficient and agammaglobulinemic sera, respectively, mean reductions in colony-forming units of 94 and 95% were seen for fresh clinical isolates, whereas strain 090 was not killed by polymorphonuclear leukocytes in the presence of these sera. All strains required a considerable amount of specific antibody for alternative pathwaymediated opsonophagocytosis. That opsonophagocytic killing of clinical type Ia isolates was mediated by the classical pathway in a nonantibody-dependent fashion was shown when MgEGTA chelation of agammaglobulinernic serum or use of serum deficient in C2 resulted in bacterial growth. The addition of C2 to C2-deficient serum restored bactericidal activity of this serum. These experiments indicate that substances other than the exposed surface of the type Ta capsular polysac-

Deficient Classical Complement Pathway Activity in Newborn Sera

“…1). Depression of bactericidal activity by these neonatal sera did not occur as the result of low specific antibody concentration, a finding which is consistent with the antibodyindependent mechanism of complement activation demonstrated previously for type Ia, group B streptococci (2,8).…”

“…Few studies have compared the functional capacity of the classical pathway for a pathogen common in the neonate with the degree of depression of individual classical pathway components. We have shown previously that bactericidal activity in adult sera for a variety of clinical isolates of type Ia, group B streptococci was mediated by the classical complement pathway in a non-antibody dependent fashion (2). Both adult sera deficient in specific antibody and agammaglobulinemic serum, which had no detectable antibody to the capsular polysaccharide antigen of type la, group B Streptococcus supported efficient bactericidal activity for each of 18 clinical type Ia, group B streptococcal isolates tested.…”

“…The type Ia, group B streptococcal isolate employed in the present studies promoted significant consumption of C4 and C3 and efficiently transferred C1 in the presence of agammaglobulinemic serum as a complement source (8). In contrast to other bacteria for which antibody-independent classical pathway activation has been described (for example, the galactose epimerase-deficient mutant E. coli J5 (3,4), and serum-sensitive Klebsiella pneumoniae strains (13), and a wild type and mutant strains of Salmonella minnesota (5)) this mechanism of complement activation is common to each of wide variety of clinical type Ia, group B streptococcal isolates tested (2). With the exception of one maternal-neonatal serum pair which contained a high concentration of specific antibody to the native capsular antigen of type Ia, group B Streptococcus, all sera tested had very low levels of type-specific antibody.…”

“…Type Ia, group B streptococcal strain, 5 15, was isolated from the blood of an infected neonate. This strain has been shown previously to be representative among 18 fresh clinical type Ia, group B streptococcal isolates for which opsonophagocytic requirements were determined in agammaglobulinemic and normal adult sera (2). These strains required the classical complement pathway for opsonophagocytosis and were not dependent upon the presence of specific antibody for initiation of classical pathway activity.…”

The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways

“…Serum deficient in anti-capsular IgG can still trigger significant phagocytic killing of GBS by a process involving complement activation that requires Ca 2+ and Mg 2+ and is hence AP-independent (32,33). It is therefore presumable that these bacteria have evolved additional virulence factors counteracting the activation of the CP or LP.…”