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

Fariza Shams,Karl G Wooldridge,Neil J Oldfield,David P J Turner,Si Kei Lai,Sarfraz A Tunio

doi:10.1002/mbo3.331

Fariza Shams, Karl G Wooldridge + Show 4 more

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https://doi.org/10.1002/mbo3.331

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Journal: MicrobiologyOpen	Publication Date: Jan 5, 2016
Citations: 15	License type: CC BY 4.0

Affiliation: University of Nottingham

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.

Highlights

Neisseria meningitidis is a prominent cause of bacterial meningitis and severe sepsis
We previously reported that FBA is a nonessential, surface-localized protein in N. meningitidis, which belongs to the Class II subfamily of FBAs (Tunio et al 2010b)
We demonstrate that: FBA is present on the surface of pathogenic and nonpathogenic species of neisseriae; aldolase activity is not required for cell surface localization or anchoring of FBA; and that FBA binds human plg, principally via the C-terminal lysine residue

Summary

Introduction

Neisseria meningitidis is a prominent cause of bacterial meningitis and severe sepsis. Diverse bacterial factors, involved in adhesion, invasion, dissemination, and protection of the organism from the innate human immune system, are expressed by N. meningitidis. By definition, moonlighting proteins perform two or more biochemical functions using a single polypeptide chain (Jeffery 1999) They are enzymatically active with cytoplasmic roles in glycolysis or other metabolic pathways, or have roles in protein synthesis (elongation factor Tu) or protein stabilization and folding (DnaK), but are displayed on the bacterial surface where they perform functions unrelated to their cytoplasmic roles, often. We demonstrate that: FBA is present on the surface of pathogenic and nonpathogenic species of neisseriae; aldolase activity is not required for cell surface localization or anchoring of FBA; and that FBA binds human plg, principally via the C-terminal lysine residue

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