Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary infection by group A streptococci (GAS) takes place at either the throat or skin of the human host, often leading to pharyngitis or impetigo, respectively. Many GAS strains differ in their preference for throat and skin tissue sites. Previous epidemiological findings show that many of the strains displaying strong tropism for the skin have a high-affinity binding site for plasminogen, located within M protein (PAM), a prominent surface fibril. Plasminogen bound by PAM interacts with streptokinase, a plasminogen activator secreted by GAS, to yield bacterial-bound plasmin activity. In this study, PAM and streptokinase were tested for their roles in infection using an experimental model that closely mimics human impetigo. Inactivation of genes encoding either PAM or streptokinase led to a partial, but significant, loss of virulence in vivo, as measured by net growth of the bacteria and pathological alterations. The relative loss in virulence in vivo was greater for the streptokinase mutant than for the PAM mutant. However, the PAM mutant, but not the streptokinase mutant, displayed a partial loss in resistance to phagocytosis in vitro. The combined experimental and epidemiological data provide evidence that PAM and streptokinase play a key role in mediating skin-specific infection by GAS. In addition, secreted cysteine proteinase activity due to SpeB leads to degradation of streptokinase in stationary phase broth cultures. Since SpeB is also a determinant of tissue-specific GAS infection at the skin, direct interactions between these two proteolytic pathways may constitute an important pathogenic mechanism. An integrated model for superficial infection at the skin is presented.
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PMID:Roles of the plasminogen activator streptokinase and the plasminogen-associated M protein in an experimental model for streptococcal impetigo. 1248 Aug 97

The plasminogen activator streptokinase has been proposed to be a key component of a complex mechanism that promotes skin invasion by Streptococcus pyogenes. This study was designed to compare ska gene message and protein levels in wild-type M1 serotype isolate 1881 and a more invasive variant recovered from the spleen of a lethally infected mouse. M1 isolates selected for invasiveness demonstrated enhanced levels of active plasminogen activator activity in culture. This effect was due to a combination of increased expression of the ska gene and decreased expression of the speB gene. The speB gene product, SpeB, was found to efficiently degrade streptokinase in vitro.
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PMID:Mouse skin passage of Streptococcus pyogenes results in increased streptokinase expression and activity. 1476 14