Clostridium perfringens Delta toxin targets CD9 to drive NEC and brain injury.

Delta toxin–positive Clostridium perfringens is linked to severe, fatal NEC in preterm infants and recapitulates intestinal necrosis plus acute cerebral injury in mice.

• Why it matters: NEC in preterm infants often causes mortality and long-term neurodevelopmental impairment, but the specific microbial factors driving gut and brain pathology are unclear.
• What they did: The study identified Delta toxin–containing Clostridium perfringens in severe/fatal NEC microbiomes, then used mice infected with Delta-toxin–positive strains or exposed to Delta toxin, plus a genome-wide CRISPR screen to implicate CD9.
• The result: Delta toxin targets macrophages, activates inflammasome signaling and pyroptosis, and CD9 ablation in systemic/myeloid compartments protects against toxin-induced lethality, blood-brain barrier dysfunction, and multiorgan injury; a neutralizing anti-Delta toxin monoclonal antibody also protects.