Fructose‐1,6‐bisphosphate aldolase of Neisseria meningitidis binds human plasminogen via its C‐terminal lysine residue

Abstract

Neisseria meningitidis is a leading cause of fatal sepsis and meningitis worldwide. As for commensal species of human neisseriae, N. meningitidis inhabits the human nasopharynx and asymptomatic colonization is ubiquitous. Only rarely does the organism invade and survive in the bloodstream leading to disease. Moonlighting proteins perform two or more autonomous, often dissimilar, functions using a single polypeptide chain. They have been increasingly reported on the surface of both prokaryotic and eukaryotic organisms and shown to interact with a variety of host ligands. In some organisms moonlighting proteins perform virulence‐related functions, and they may play a role in the pathogenesis of N. meningitidis. Fructose‐1,6‐bisphosphate aldolase (FBA) was previously shown to be surface‐exposed in meningococci and involved in adhesion to host cells. In this study, FBA was shown to be present on the surface of both pathogenic and commensal neisseriae, and surface localization and anchoring was demonstrated to be independent of aldolase activity. Importantly, meningococcal FBA was found to bind to human glu‐plasminogen in a dose‐dependent manner. Site‐directed mutagenesis demonstrated that the C‐terminal lysine residue of FBA was required for this interaction, whereas subterminal lysine residues were not involved.

The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella

“…Pneumococcal FBA is involved in the binding to human lung epithelial A549 cells via an interaction with a receptor belonging to the cadherin family. In N. meningitidis , FBA is not essential but is required for optimal adhesion to both human epithelial and endothelial cells 62 , 63 . The recent detection of FBA in the cell wall fraction of Coxiella burnetii 64 and the identification of FBA orthologues in other pathogenic Gram-negative bacterial species, suggest that translocation of FBA to the Gram-negative cell envelope might constitute a more generalized phenomenon.…”

Clone, expression and plasminogen binding property of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis

“…FbA has been proven to be a human plasminogen binding and activating protein in parasite (Ramajo-Hernandez et al, 2007;Lorenzatto et al, 2012) and non-parasite (Crowe et al, 2003;Shams et al, 2016). The phenomenon of human plasminogen binding is commonly found in bacteria (Boyle & Lottenberg, 1997), fungi (Crowe et al, 2003), protozoa (Mundodi et al, 2008;Gomez-Arreaza et al, 2011;Figuera et al, 2013), and helminth infection (Jolodar et al, 2003;Bernal et al, 2004;Ramajo-Hernandez et al, 2007;de la Torre-Escudero et al, 2010).…”

“…In our study, plasminogen binding property of three rCsFbAs could be effectively inhibited by lysine analog ε-ACA ( Figure 5A and C-E), implying that CsFbAs possibly contain carboxy-terminal lysine residues as the sites for plasminogen binding. Terminal lysine of Neisseria meningitidis FbA replaced by alanine did not completely block the binding and the residual binding was still blocked by lysine analog ε-ACA, suggesting that several lysine residues within FbA might contribute to the interaction with plasminogen (Shams et al, 2016). Thus, it is speculated that plasminogen binding affinity of rCsFbAs may depend on the density of terminal lysine sites.…”

Fructose-1,6-bisphosphate aldolase encoded by a core gene of Mycoplasma hyopneumoniae contributes to host cell adhesion

“…FBA from Streptococcus suis , which is reasonably well conserved among S. suis strains, was verified as an immunogenic cell wall protein, suggesting it could be developed as a vaccine candidate [ 49 ]. FBA of Neisseria meningitidis is localised both in the cytoplasm and the outer membrane, and is required for adhesion to human cells [ 50 ] by binding to plasminogen [ 51 ]. In Mycobacterium tuberculosis , FBA is required for survival during the chronic phase of mouse infection [ 52 ].…”