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The moonlighting peroxiredoxin-glutaredoxin in Neisseria meningitidis binds plasminogen via a C-terminal lysine residue and contributes to survival in a whole blood model.
- Source :
-
Microbial pathogenesis [Microb Pathog] 2020 Feb; Vol. 139, pp. 103890. Date of Electronic Publication: 2019 Nov 23. - Publication Year :
- 2020
-
Abstract
- 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 ε-aminocapronic acid. rPrx5-Grx derivatives bearing a substituted C-terminal lysine residue (rPrx5-Grx <superscript>K244A</superscript> ), but not the active site cysteine residue (rPrx5-Grx <superscript>C185A</superscript> ) or the sub-terminal rPrx5-Grx <superscript>K230A</superscript> 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.<br />Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Subjects :
- Enzyme-Linked Immunosorbent Assay
Glutaredoxins chemistry
Glutaredoxins genetics
Humans
Hydrogen Peroxide metabolism
Meningococcal Infections diagnosis
Meningococcal Infections mortality
Mutation
Peroxiredoxins chemistry
Peroxiredoxins genetics
Plasminogen chemistry
Prognosis
Protein Binding
Protein Interaction Domains and Motifs
Glutaredoxins metabolism
Host-Pathogen Interactions
Meningococcal Infections metabolism
Meningococcal Infections microbiology
Neisseria meningitidis physiology
Peroxiredoxins metabolism
Plasminogen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-1208
- Volume :
- 139
- Database :
- MEDLINE
- Journal :
- Microbial pathogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 31765768
- Full Text :
- https://doi.org/10.1016/j.micpath.2019.103890