title: Thioredoxins and Methionine Sulfoxide Reductases in the Pathophysiology of Pneumococcal Meningitis.
abstract: Pneumococcal proteins involved in the resistance against oxidative stress are present in all strains and therefore are potential antigens that could be suitable for new therapies and/or vaccines. Their role in the pathogenesis of pneumococcal meningitis has not been addressed.
  
  
  
  We investigated the individual contributions of extracellular thioredoxin lipoproteins (Etrx1 and Etrx2) and the intracellular and extracellular methionine sulfoxide reductases (SpMsrAB1 and SpMsrAB2, respectively) in the progression and outcome of pneumococcal meningitis, using Kaplan-Meier survival curves, bacteriological and histological studies, and measurements of proinflammatory mediators.
  
  
  
  The absence of Etrx1, Etrx2, or SpMsrAB1 moderately attenuated virulence as compared to the wild-type strain but did not significantly affect bacterial growth in the brain and bloodstream. Loss of function of SpMsrAB2 alone, both Etrx proteins, or both SpMsrAB proteins resulted in a less severe course of infection, with low numbers of animals dying of infection, a lower risk of associated meningeal inflammation, and reduced bacterial densities in the cerebellum, blood, and spleen.
  
  
  
  Our data support the importance of the extracellular redox repair system in virulence and its potential as a target for the design of new antimicrobials and vaccine formulations against Streptococcus pneumoniae.
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ribes
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Abdullah
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany.
authors.forename: Malek
authors.initials: M
authors.lastname: Saleh
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen.
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen Department of Geriatrics, Evangelisches Krankenhaus Göttingen-Weende.
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
authors.affiliation: Department Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, Ernst Moritz Arndt University of Greifswald, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D000818:Animals; D001769:Blood / Q000382:microbiology; D001921:Brain / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000473:pathology*; D051150:Methionine Sulfoxide Reductases / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013154:Spleen; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000472:pathogenicity*; D016019:Survival Analysis; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D013879:Thioredoxins; D051150:Methionine Sulfoxide Reductases
keywords: CNS infection; IFN-γ; IL-12/IL-23p40; MsrAB; Streptococcus pneumoniae; oxidative stress; thioredoxins