Biological Functions of the Secretome of Neisseria meningitidis

Abstract

Neisseria meningitidis is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of N. meningitidis and focus on the functions of the secreted proteins.

Suppression of Intestinal Epithelial Cell Chemokine Production by Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0389 Is Mediated by Secreted Bioactive Molecules

“…Some pathogenic bacteria also secrete proteins and other molecules with bioactivity, suggesting this is an important route of microbe-host communication. For example, several species of Neisseria, including Neisseria meningitidis , secrete multiple proteins and other small molecules responsible for communication with the host ( 48 , 49 ). Monosaccharide heptose-1,7-bisphosphate (HBP), a metabolic intermediate in LPS synthesis is released into the CFS of N. meningitidis , interacts with the novel PRR TRAF-interacting protein with forkhead-associated domain (TIFA) to activate NFκB and induce macrophage cytokine production ( 50 ).…”

Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting

“…In theory, the increased negative charge of the bacterial surface increases repulsion forces between the bacterial cell surface and the host cell disrupting the initial colonization interactions of the bacterial adhesins with host cell receptors. A second possibility is that the change to lipid A structure in addition to surface charge may also affect the positioning and function of outer membrane adhesins thus affecting attachment and invasion ( Tommassen and Arenas, 2017 ). Although this effect on attachment has been observed in cell monolayer models of infection for both MC and GC, eptA mutants of GC were as efficient as wild-type strains in colonizing the urogenital tract of the female mouse model ( Packiam et al, 2014 ).…”

Proteomics, Bioinformatics and Structure-Function Antigen Mining For Gonorrhea Vaccines

“…NGO2111 is homologous to the Nm surface lipoprotein assembly modulator Slam2, which is involved in translocating the hemoglobin-haptoglobin utilization protein to the cell surface (174). Slam2 is highly conserved amongst Neisseria isolates and is not found in E. coli (175, 176). Ng Slam2 contains a signal peptide and a 14-stranded β-barrel domain, which has also been annotated as a DUF560 domain (Figure 3D; 147, 176).…”