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: Aljannat MAK; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Oldfield NJ; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Albasri HM; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Dorrington LKG; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Ohri RL; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Wooldridge KG; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK., Turner DPJ; School of Life Sciences, University of Nottingham, Nottingham, NG7 2RD, UK. Electronic address: david.turner@nottingham.ac.uk.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2020 Feb; Vol. 139, pp. 103890. Date of Electronic Publication: 2019 Nov 23.
DOI: 10.1016/j.micpath.2019.103890
Abstrakt: 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 K244A ), but not the active site cysteine residue (rPrx5-Grx C185A ) or the sub-terminal rPrx5-Grx K230A 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.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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