RESUMEN
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.
Asunto(s)
Glutarredoxinas/metabolismo , Interacciones Huésped-Patógeno , Infecciones Meningocócicas/metabolismo , Infecciones Meningocócicas/microbiología , Neisseria meningitidis/fisiología , Peroxirredoxinas/metabolismo , Plasminógeno/metabolismo , Ensayo de Inmunoadsorción Enzimática , Glutarredoxinas/química , Glutarredoxinas/genética , Humanos , Peróxido de Hidrógeno/metabolismo , Infecciones Meningocócicas/diagnóstico , Infecciones Meningocócicas/mortalidad , Mutación , Peroxirredoxinas/química , Peroxirredoxinas/genética , Plasminógeno/química , Pronóstico , Unión Proteica , Dominios y Motivos de Interacción de ProteínasRESUMEN
MenACWY conjugate vaccination was recently introduced in the United Kingdom for adolescents and young adults to reduce disease from infection by Neisseria meningitidis group W. We conducted a cross-sectional meningococcal carriage study in first-year UK university students. Despite 71% MenACWY vaccine coverage, carriage of group W increased substantially.