Analysis Biomolecular Interactions of Full-length NADase and SLO by BLI (CAT#: STEM-MB-0177-CJ)

Introduction

SLO, a cholesterol-dependent cytolysin (CDC), acts, at least in part, by disruption of eukaryotic cell membranes. Like other CDCs, it oligomerizes on the surface of cells and inserts into the membrane to create a large pore. Sufficient damage to the cell membrane results in cell death, as demonstrated in studies using macrophages, neutrophils, keratinocytes, and red blood cells. At sublytic concentrations, SLO has been shown to inhibit degranulation of neutrophils. SLO thus contributes to bacterial evasion of phagocytosis and resistance to killing by the immune system.

NADase can cleave NAD to produce nicotinamide and adenosine diphosphoribose in mammalian cells, thereby promoting cytotoxicity through depletion of energy stores. Its subunit architecture includes an N-terminal translocation domain and a C-terminal catalytic domain that harbors NADase activity.

SLO and NADase are known to be intimately associated with one another during infection. It is thought that SLO mediates translocation of NADase across the cell membrane in a mechanism that is independent of pore formation. The pathogen is better able to survive after internalization into keratinocytes in the presence of both SLO and NADase through inhibition of maturation of autophagosomes that contain intracellular GAS.