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.

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: Nov 24, 2020
• 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
• Contract Date: Nov 27, 2019