L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily throughN-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway

Abstract

Group B streptococci (GBS) are the most common cause of neonatal sepsis and meningitis. Most infants who are colonized with GBS at birth do not develop invasive disease, although many of these uninfected infants lack protective levels of capsular polysaccharide (CPS)-specific antibody. The lectin pathway of complement is a potential mechanism for initiating opsonization of GBS with CPS-specific antibody-deficient serum. In this study, we determined whether mannose-binding lectin (MBL)/MBL-associated serine protease (MASP) complexes and L-ficolin/MASP complexes bind to different strains of GBS to activate the lectin pathway, and we identified the molecules recognized by lectins on the GBS surface. We found that MBL did not bind to any GBS examined, whereas L-ficolin bound to GBS cells of many serotypes. L-ficolin binding to GBS cells correlated with the CPS content in serotypes Ib, III (restriction digestion pattern types III-2 and III-3), and V but not with the group B-specific polysaccharide (GBPS) content or with the lipoteichoic acid (LTA) content. L-ficolin bound to purified CPS and GBPS in a concentration-dependent manner but not to purified LTA. All strains to which L-ficolin/MASP complexes bound consumed C4. When N-acetylneuraminic acid (NeuNAc) was selectively removed from GBS cells by treatment with neuraminidase, the reduction in L-ficolin binding was correlated with the amount of NeuNAc removed. Additionally, L-ficolin was able to bind to wild-type strains but was able to bind only weakly to unencapsulated mutants and a mutant strain in which the CPS lacks NeuNAc. We concluded that L-ficolin/MASP complexes bind to GBS primarily through an interaction with NeuNAc of CPS.

Mannose-Binding Lectin (MBL) Facilitates Opsonophagocytosis of Yeasts but Not of Bacteria despite MBL Binding

“…L-ficolin is the most intensively studied ficolin. Several articles describe the binding of L-ficolin to various capsulated S. aureus serotypes, capsulated group B streptococci, and capsulated S. pneumoniae, but not to noncapsulated strains (23,34). Upon binding to the capsulated group B streptococci, L-ficolin/ MASP complex-dependent C4 consumption was observed.…”

L-Ficolin and Capsular Polysaccharide-Specific IgG in Cord Serum Contribute Synergistically to Opsonophagocytic Killing of Serotype III and V Group B Streptococci

“…GBS isolates used in this study have been characterized previously (1,13,36) and are listed in Table 1.…”

“…The L-ficolin-mediated lectin pathway of the complement system (24,25) is a potential mechanism for initiating opsonization of GBS in serotype-specific IgG-deficient serum, because L-ficolin binds CPS purified from serotype Ia, Ib, III, V, VI, and VIII GBS through an interaction with the N-acetylneuraminic acid (NeuNAc) component of CPS. L-ficolin also binds to intact GBS from serotypes Ib, III, V, VI, and VIII, and bacteria to which L-ficolin binds consume complement C4 (1). Binding of L-ficolin to serotype III GBS results in C3b deposition on the bacteria, and C3b deposition is further enhanced by addition of serotype III-specific IgG2, leading to increased opsonophagocytic killing (2).…”

Commercially Available Complement Component-Depleted Sera Are Unexpectedly Codepleted of Ficolin-2

“…This family of proteins functions as pattern recognition molecules with an affinity for acetylated ligands (1). Ficolin-2 has been recently shown to be important during pneumococcal pathogenesis (2)(3)(4) and is known to bind to many other significant human pathogens (2,5,6). Moreover, ficolin-2 and -3 have been implicated in many different disease pathologies, such as transplant reperfusion injury (7), clearance of apoptotic cells (8,9), and even preeclampsia (10).…”