Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification

• Published in: Nature communications 2018-08, Vol.9 (1), p.3398-16, Article 3398
• Main Authors: Pathak, Anuj, Bergstrand, Jan, Sender, Vicky, Spelmink, Laura, Aschtgen, Marie-Stephanie, Muschiol, Sandra, Widengren, Jerker, Henriques-Normark, Birgitta
• Format: Article
• Language: English
• Subjects: 13; 13/106; 13/31; 14; 14/1; 14/28; 14/63; 692/420/254; 692/420/2780/262; 82/103; 82/83; A549 Cells; Adhesins; Amino Acid Sequence; Amplification; Bacterial Capsules - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Cell Adhesion; Cell Division; Cell surface; Colonization; Complement C3b - metabolism; Complement component C3; Complement component C3b; Complement factor H; Complement Factor H - metabolism; Complement Membrane Attack Complex - metabolism; Complement system; Deposition; Epithelial Cells - cytology; Epithelial Cells - metabolism; Functional analysis; Humanities and Social Sciences; Humans; Localization; Medicin och hälsovetenskap; Models, Biological; multidisciplinary; Mutation - genetics; Opsonin Proteins - metabolism; Opsonization; Opsonophagocytosis; Phagocytosis; Polysaccharides; Protein Binding; Protein Sorting Signals; Proteins; Science; Science (multidisciplinary); Septum; Spatial discrimination; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - cytology; Streptococcus pneumoniae - metabolism; Streptococcus pneumoniae - ultrastructure; Virulence
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05494-w

Streptococcus pneumoniae evades C3-mediated opsonization and effector functions by expressing an immuno-protective polysaccharide capsule and Factor H (FH)-binding proteins. Here we use super-resolution microscopy, mutants and functional analysis to show how these two defense mechanisms are functionally and spatially coordinated on the bacterial cell surface. We show that the pneumococcal capsule is less abundant at the cell wall septum, providing C3/C3b entry to underlying nucleophilic targets. Evasion of C3b deposition at division septa and lateral amplification underneath the capsule requires localization of the FH-binding protein PspC at division sites. Most pneumococcal strains have one PspC protein, but successful lineages in colonization and disease may have two, PspC1 and PspC2, that we show affect virulence differently. We find that spatial localization of these FH-recruiting proteins relative to division septa and capsular layer is instrumental for pneumococci to resist complement-mediated opsonophagocytosis, formation of membrane-attack complexes, and for the function as adhesins. Streptococcus pneumoniae evades the action of the complement system by expressing an immuno-protective polysaccharide capsule as well as Factor H-binding proteins. Here, Pathak et al. show that these two defence mechanisms are functionally and spatially coordinated on the bacterial cell surface.