Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031350 (pharyngitis)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Streptococcus pyogenes is an important pathogen that causes pharyngitis, sepsis, and rheumatic fever. Cell-associated streptococcal C5a peptidase (ScpA) protects S. pyogenes from phagocytosis and has been suggested to interrupt host defenses by enzymatically cleaving complement C5a, a major factor in the accumulation of neutrophils at sites of infection. How S. pyogenes recognizes and binds to C5a, however, is unclear. We detected a C5a-binding protein in 8 M urea extracts of S. pyogenes by ligand blotting using biotinylated C5a. Searching of genome databases showed that the C5a-binding protein is identical to the streptococcal plasmin receptor (Plr), also known as streptococcal surface dehydrogenase (SDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In the present study we identified a novel function of this multifunctional protein. Western blotting and immunofluorescence microscopy with anti-Plr/SDH/GAPDH showed that Plr/SDH/GAPDH is located on the bacterial surface and released into the culture supernatant. Next, we examined whether the streptococcal Plr/SDH/GAPDH inhibits the biological effects of C5a on human neutrophils. We found that soluble Plr/SDH/GAPDH inhibits C5a-activated chemotaxis and H2O2 production. Furthermore, our results suggested that soluble Plr/SDH/GAPDH captures C5a, inhibiting its chemotactic function. Also, cell-associated Plr/SDH/GAPDH and ScpA were both necessary for the cleavage of C5a on the bacterial surface. Together, these results indicate that the multifunctional protein Plr/SDH/GAPDH has additional functions that help S. pyogenes escape detection by the host immune system.
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PMID:Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. 1656 20

Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways.
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PMID:Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes. 2602 91