RGD Reference Report - Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections. - Rat Genome Database

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Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections.

Authors: Peetermans, Marijke  Vanassche, Thomas  Liesenborghs, Laurens  Claes, Jorien  Vande Velde, Greetje  Kwiecinksi, Jakub  Jin, Tao  De Geest, Bart  Hoylaerts, Marc F  Lijnen, Roger H  Verhamme, Peter 
Citation: Peetermans M, etal., BMC Microbiol. 2014 Dec 17;14:310. doi: 10.1186/s12866-014-0310-7.
RGD ID: 36174009
Pubmed: PMID:25515118   (View Abstract at PubMed)
PMCID: PMC4274676   (View Article at PubMed Central)
DOI: DOI:10.1186/s12866-014-0310-7   (Journal Full-text)


BACKGROUND: Staphylococcus aureus (S. aureus) is a frequent cause of skin and soft tissue infections. A unique feature of S. aureus is the combined presence of coagulases that trigger fibrin formation and of the plasminogen activator staphylokinase (SAK). Whereas the importance of fibrin generation for S. aureus virulence has been established, the role of SAK remains unclear. We studied the role of plasminogen activation by SAK in a skin infection model in mice and evaluated the impact of alpha-2-antiplasmin (α2AP) deficiency on the spreading and proteolytic activity of S. aureus skin infections. The species-selectivity of SAK was overcome by adenoviral expression of human plasminogen. Bacterial spread and density was assessed non-invasively by imaging the bioluminescence of S. aureus Xen36.
RESULTS: SAK-mediated plasmin activity increased the local invasiveness of S. aureus, leading to larger lesions with skin disruption as well as decreased bacterial clearance by the host. Even though fibrin and bacterial surfaces protected SAK-mediated plasmin activity from inhibition by α2AP, the deficiency of α2AP resulted in increased bacterial spreading. SAK-mediated plasmin also induced secondary activation of gelatinases, shown both in vitro and in lesions from the in vivo model.
CONCLUSION: SAK contributes to the phenotype of S. aureus skin infections by enhancing bacterial spreading as a result of fibrinolytic and proteolytic activation.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SERPINF1HumanStaphylococcal Skin Infections severityISOSerpinf1 (Mus musculus) RGD 
Serpinf1RatStaphylococcal Skin Infections severityISOSerpinf1 (Mus musculus) RGD 
Serpinf1MouseStaphylococcal Skin Infections severityIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpinf1  (serpin family F member 1)

Genes (Mus musculus)
Serpinf1  (serine (or cysteine) peptidase inhibitor, clade F, member 1)

Genes (Homo sapiens)
SERPINF1  (serpin family F member 1)


Additional Information