Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0031350 (
pharyngitis
)
2,405
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Group A
Streptococcus
(GAS) is a human pathogen causing a wide spectrum of diseases, from mild
pharyngitis
to life-threatening necrotizing fasciitis. GAS has been shown to evade host immune killing by invading host cells. However, how GAS resists intracellular killing by endothelial cells is still unclear. In this study, we found that strains NZ131 and A20 have higher activities of NADase and intracellular multiplication than strain SF370 in human endothelial cells (HMEC-1). Moreover,
nga
mutants of NZ131 (SW957 and SW976) were generated to demonstrate that NADase activity is required for the intracellular growth of GAS in endothelial cells. We also found that intracellular levels of NAD
+
and the NAD
+
/
NADH
ratio of NZ131-infected HMEC-1 cells were both lower than in cells infected by the
nga
mutant. Although both NZ131 and its
nga
mutant were trapped by LC3-positive vacuoles, only
nga
mutant vacuoles were highly co-localized with acidified lysosomes. On the other hand, intracellular multiplication of the
nga
mutant was increased by bafilomycin A1 treatment. These results indicate that NADase causes intracellular NAD
+
imbalance and impairs acidification of autophagosomes to escape autophagocytic killing and enhance multiplication of GAS in endothelial cells.
...
PMID:NAD-Glycohydrolase Depletes Intracellular NAD
+
and Inhibits Acidification of Autophagosomes to Enhance Multiplication of Group A
Streptococcus
in Endothelial Cells. 3012 94
