1. Översiktlig projektbeskrivning

Sammanfattning av projektet

Staphylokinase (SAK) is one of bacterial plasminogen activators produced by a great majority of clinical S. aureus isolates. However, the role of SAK as a driving force in staphylococcal infections is still largely unknown.In this project, the role of SAK in stpahylococcal septic arthritis and sepsis will be intensively studied. We have constructed a single copy integration vector pCL84 carrying sak gene integrated in two forms, linked to its own promoter and also fused to the promoter and translation initiation signals of the protein A gene. The latter modification induces SAK over-expression. S. aureus LS-1 has been transduced with those vectors. Since staphylokinase cannot interact with murine plasminogen, human plg transgenic mice will be injected i.v. with SAK transgenic s.aureus strains to induce staphylococcal septic arthritis and sepsis. The frequency and severity of arthritis, mortality rate, bacterial load in kidneys, and weight loss will be monitored during the infection. In vitro matrigel assay will be used to assess the invasive capacity of SAK transgenic strains. Understanding the role of staphylokinase in staphylococcal infections will enable better insight to the pathogenesis of disease. Targeting bacterial plasminogen activators might be a potential therapeutic strategy in staphylococcal infections.

Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva ämnesområdet

Inlagda MeSH-termer

Staphylococcus aureus

Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.

Infection

Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.

Models, Animal

Non-human animals, selected because of specific characteristics, for use in experimental research, teaching, or testing.

Fibrinolysis

The natural enzymatic dissolution of FIBRIN.

Academic Dissertations

Works consisting of formal presentations made usually to fulfill requirements for an academic degree.

Projektets delaktighet i utbildning

Avhandling
D-uppsats / Magisterexamen
C-uppsats / Kandidatexamen
ST-läkarutbildning
Annan utbildning
Ej del i utbildning

3. Processen och projektets redovisning

Pågående aktiviteter

Planering och förberedelse före datainsamling
Datainsamling pågår
Analys av insamlade data pågår
Författande av skriftlig redovisning / publikation pågår
En eller flera publikationer från projektet är publicerade
Slutfört och inget mer görs inom ramen för detta projekt

Projektstart (när planeringen påbörjas och börjar dokumenteras skriftligt)

2009-01-01

Datum för påbörjande av datainsamling

2010-12-30

Datum då projektet är slutrapporterat

2010-12-31

Publikationer från detta projekt

1. Activation of plasminogen by staphylokinase reduces the severity of Staphylococcus aureus systemic infection.
   Kwieci Jakub, Josefsson Elisabet, Mitchell Jennifer, Higgins Judy, Magnusson Mattias, Foster Timothy, Jin Tao, Bokarewa Maria.
   J Infect Dis. 2010:202(7):1041-9.[Source: PubMed®]
   [Links: PMID: 20726765 | DOI länk]
2. Tranexamic acid, an inhibitor of plasminogen activation, aggravates staphylococcal septic arthritis and sepsis.
   K Marcin, Anäkkälä Nicola, Wang Wanzhong, Lange Stefan, Jonsson Ing-Marie, Tarkowski Andrej, Jin Tao.
   Scand J Infect Dis. 2010:42(5):351-8.[Source: PubMed®]
   [Links: PMID: 20100112 | DOI länk]

Tillämpning av resultat - tidsaspekt (projektledarens bedömning)

Resultaten kommer sannolikt att tillämpas inom 5 år från projektslut.

Tillämpning av resultat - genomslag (projektledarens bedömning)

Internationellt (i flera länder)

Tillämpning av resultat - beskrivning

We found that human plg transgenic mice inoculated with SAK-expressing strains displayed significantly reduced mortality, less weight loss, and lower bacterial loads in kidneys than did the wild-type mice. No difference in the severity of sepsis was observed between transgenic and wild-type mice infected with a SAK-deficient strain. Our results suggest that expression of SAK followed by activation of plg alleviates the course of S. aureus sepsis. Our finding casts light on the potential therapeutic strategies against S. aureus sepsis by modulating bacterial fibrinolytic molecules.

4. Detaljerad projektbeskrivning

Bilagor

2010 JID SAK sepsis.pdf

Publication 1
Filstorlek: 472 kB

2010 cyklokapron.pdf

Publication 2
Filstorlek: 113 kB