The moonlighting peroxiredoxin-glutaredoxin in Neisseria meningitidis binds plasminogen via a C-terminal lysine residue and contributes to survival in a whole blood model
| Autor: | Louise K.G. Dorrington, Hibah M. Albasri, David P. J. Turner, Neil J. Oldfield, Karl G. Wooldridge, Radhica L. Ohri, Mahab A.K. Aljannat |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Protein moonlighting 030106 microbiology Mutant Lysine Enzyme-Linked Immunosorbent Assay Neisseria meningitidis medicine.disease_cause Microbiology law.invention 03 medical and health sciences Residue (chemistry) law medicine Humans Protein Interaction Domains and Motifs Glutaredoxins Whole blood Chemistry Plasminogen Hydrogen Peroxide Peroxiredoxins Prognosis Meningococcal Infections 030104 developmental biology Infectious Diseases Host-Pathogen Interactions Mutation Recombinant DNA Peroxiredoxin Protein Binding |
| Zdroj: | Microbial Pathogenesis. 139:103890 |
| ISSN: | 0882-4010 |
| DOI: | 10.1016/j.micpath.2019.103890 |
| Popis: | Neisseria meningitidis is a human-restricted bacterium that can invade the bloodstream and cross the blood-brain barrier resulting in life-threatening sepsis and meningitis. Meningococci express a cytoplasmic peroxiredoxin-glutaredoxin (Prx5-Grx) hybrid protein that has also been identified on the bacterial surface. Here, recombinant Prx5-Grx was confirmed as a plasminogen (Plg)-binding protein, in an interaction which could be inhibited by the lysine analogue e-aminocapronic acid. rPrx5-Grx derivatives bearing a substituted C-terminal lysine residue (rPrx5-GrxK244A), but not the active site cysteine residue (rPrx5-GrxC185A) or the sub-terminal rPrx5-GrxK230A lysine residue, exhibited significantly reduced Plg-binding. The absence of Prx5-Grx did not significantly reduce the ability of whole meningococcal cells to bind Plg, but under hydrogen peroxide-mediated oxidative stress, the N. meningitidis Δpxn5-grx mutant survived significantly better than the wild-type or complemented strains. Significantly, using human whole blood as a model of meningococcal bacteremia, it was found that the N. meningitidis Δpxn5-grx mutant had a survival defect compared with the parental or complemented strain, confirming an important role for Prx5-Grx in meningococcal pathogenesis. |
| Databáze: | OpenAIRE |
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