Journal Article

Neisserial adhesin A (NadA) binds human Siglec-5 and Siglec-14 with high affinity and promotes bacterial adhesion/invasion

Merola, Marcello, Maione, Domenico, Calvaresi, Valeria, Viviani, Viola, Norais, Nathalie, d’Alterio, Liana, Bartolini, Erika, Rappuoli, Rino, Pinzuti, Irene, Faleri, Agnese, Pansegrau, Werner, Utrio Lanfaloni, Sabrina, Perrotta, Andrea, Benucci, Barbara, Spinello, Zaira, Pizza, Mariagrazia, Sampieri, Katia, Masignani, Vega, Giordano, Anna

2024

Overview

Bacteria have developed several strategies for cell colonization and immune evasion. Knowledge of the host and pathogen factors involved in these mechanisms is crucial to build efficacious countermoves. Neisserial adhesin A (NadA) is a meningococcal surface protein included in the anti-meningococcus B vaccine 4CMenB, which mediates adhesion to and invasion of epithelial cells. Although NadA has been shown to bind to other cell types, like myeloid and endothelial cells, it still remains orphan of a defined host receptor. We have identified two strong NadA interactors, Siglec-5 and Siglec-14, which are mainly expressed on myeloid cells. This showcases that NadA is an additional and key player among the Neisseria meningitidis factors targeting immune cells. We thus provide novel insights on the strategies exploited by N. meningitidis during the infection process, which can progress to a severe illness and death.

• Publisher: American Society for Microbiology
• Subject: Adhesins, Bacterial - genetics / Adhesins, Bacterial - metabolism / Amino acids / Animals / Antigens / Antigens, CD - genetics / Antigens, CD - metabolism / Antigens, Differentiation, Myelomonocytic - genetics / Antigens, Differentiation, Myelomonocytic - metabolism / Bacterial Adhesion / CHO Cells / Cricetulus / Cytokines / Endothelial cells / Epithelial cells / Epithelial Cells - immunology / Epithelial Cells - metabolism / Epithelial Cells - microbiology / Host-Microbial Interactions / Host-Pathogen Interactions / Humans / Hydrogen-deuterium exchange / Immune response / Lectins / Lectins - genetics / Lectins - immunology / Lectins - metabolism / Mass spectroscopy / Meningococcal Infections - immunology / Meningococcal Infections - microbiology / Mice / Myeloid cells / NadA receptor / Neisseria meningitidis / Neisseria meningitidis - genetics / Neisseria meningitidis - immunology / Neisseria meningitidis - metabolism / Neisseria meningitidis, Serogroup B - genetics / Neisseria meningitidis, Serogroup B - immunology / Neisseria meningitidis, Serogroup B - metabolism / Neisserial adhesin A (NadA) / Pathogens / Phosphatase / Protein arrays / Protein Binding / Proteins / Receptors, Cell Surface - genetics / Receptors, Cell Surface - metabolism / Recombinant Proteins - genetics / Recombinant Proteins - metabolism / Research Article / Sialic Acid Binding Immunoglobulin-like Lectins - genetics / Sialic Acid Binding Immunoglobulin-like Lectins - metabolism / Siglec-14 / Siglec-5 / Siglec-9 / Vaccines