Longevity & AgingBacterial Toxin Mimics Human CD38 to Deplete NAD+ in Rivals and Host Cells
Researchers identified a novel toxin domain in Pantoea ananatis bacteria that structurally mimics the human enzyme CD38, a key player in NAD+ metabolism and immune regulation. Solved at 1.6 Å resolution, the bacterial ADP-ribosyl cyclase (ARC) domain shares CD38's catalytic residues and globular fold, hydrolyzing NAD+ and NADP+ to kill both bacterial competitors and eukaryotic cells. The toxin is delivered via the Type VI Secretion System and is neutralized by a cognate immunity protein. Genomic surveys reveal CD38-like ARC domains are widespread across bacterial species, fused to diverse delivery systems including T6SS, T7SS, and CDI systems — suggesting bacteria have broadly co-opted this eukaryote-like enzymatic fold as a metabolic warfare weapon.
