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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

Aljannat, Mahab A.K.; Oldfield, Neil J.; Albasri, Hibah M.; Dorrington, Louise K.G.; Ohri, Radhica L.; Wooldridge, Karl G.; Turner, David P.J.

The moonlighting peroxiredoxin-glutaredoxin in Neisseria meningitidis binds plasminogen via a C-terminal lysine residue and contributes to survival in a whole blood model Thumbnail


Authors

Mahab A.K. Aljannat

Hibah M. Albasri

Louise K.G. Dorrington

Radhica L. Ohri

DAVID TURNER david.turner@nottingham.ac.uk
Clinical Associate Professor



Abstract

© 2019 Elsevier Ltd 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-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.

Citation

Aljannat, M. A., Oldfield, N. J., Albasri, H. M., Dorrington, L. K., Ohri, R. L., Wooldridge, K. G., & Turner, D. P. (2020). The moonlighting peroxiredoxin-glutaredoxin in Neisseria meningitidis binds plasminogen via a C-terminal lysine residue and contributes to survival in a whole blood model. Microbial Pathogenesis, 139, Article 103890. https://doi.org/10.1016/j.micpath.2019.103890

Journal Article Type Article
Acceptance Date Nov 22, 2019
Online Publication Date Nov 23, 2019
Publication Date Feb 1, 2020
Deposit Date Nov 27, 2019
Publicly Available Date Mar 28, 2024
Journal Microbial Pathogenesis
Print ISSN 0882-4010
Electronic ISSN 1096-1208
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 139
Article Number 103890
DOI https://doi.org/10.1016/j.micpath.2019.103890
Keywords Microbiology; Infectious Diseases
Public URL https://nottingham-repository.worktribe.com/output/3416432
Publisher URL https://www.sciencedirect.com/science/article/pii/S0882401019311192

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