The study investigates the role of peptidylarginine deiminase 4 (PAD4) in neutrophil extracellular traps (NETs) and their antibacterial function. PAD4 knockout mice were used to demonstrate that PAD4 is essential for NET formation and subsequent bacterial killing. PAD4−/− neutrophils fail to form NETs in response to chemokines or bacteria and are deficient in bacterial killing. In a mouse model of necrotizing fasciitis, PAD4−/− mice are more susceptible to bacterial infection due to a lack of NET formation. The results suggest that PAD4 primarily plays a role in chromatin decondensation to form NETs rather than increasing histone-mediated bacterial killing. The study defines the role of histone hypercitrullination in innate immunity during bacterial infection.The study investigates the role of peptidylarginine deiminase 4 (PAD4) in neutrophil extracellular traps (NETs) and their antibacterial function. PAD4 knockout mice were used to demonstrate that PAD4 is essential for NET formation and subsequent bacterial killing. PAD4−/− neutrophils fail to form NETs in response to chemokines or bacteria and are deficient in bacterial killing. In a mouse model of necrotizing fasciitis, PAD4−/− mice are more susceptible to bacterial infection due to a lack of NET formation. The results suggest that PAD4 primarily plays a role in chromatin decondensation to form NETs rather than increasing histone-mediated bacterial killing. The study defines the role of histone hypercitrullination in innate immunity during bacterial infection.