PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps (NETs). This study shows that PAD4 is required for NET formation and bacterial killing. PAD4 knockout mice exhibit impaired NET formation and reduced bacterial killing. PAD4 is involved in histone hyper-citrullination, which facilitates chromatin decondensation necessary for NET formation. PAD4-deficient neutrophils fail to form NETs upon stimulation with chemokines or bacteria, and are deficient in bacterial killing. In a mouse model of necrotizing fasciitis, PAD4-deficient mice are more susceptible to infection due to the lack of NET formation. The study also shows that citrullination decreases the bacterial killing activity of histones and nucleosomes, suggesting that PAD4's role is in chromatin decondensation rather than increasing histone-mediated killing. PAD4 is essential for histone citrullination and chromatin decondensation during NET formation. PAD4 knockout mice show reduced histone citrullination and NET formation. PAD4 is required for NET-mediated bacterial killing, as shown by experiments with S. flexneri and M1 GAS. PAD4-deficient neutrophils have reduced ability to kill bacteria, especially when NET formation is inhibited. The study highlights the importance of PAD4 in innate immunity and NET-mediated bacterial killing. PAD4 is a key factor in the formation of NETs and their antibacterial function. The results define a role for histone hypercitrullination in innate immunity during bacterial infection.PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps (NETs). This study shows that PAD4 is required for NET formation and bacterial killing. PAD4 knockout mice exhibit impaired NET formation and reduced bacterial killing. PAD4 is involved in histone hyper-citrullination, which facilitates chromatin decondensation necessary for NET formation. PAD4-deficient neutrophils fail to form NETs upon stimulation with chemokines or bacteria, and are deficient in bacterial killing. In a mouse model of necrotizing fasciitis, PAD4-deficient mice are more susceptible to infection due to the lack of NET formation. The study also shows that citrullination decreases the bacterial killing activity of histones and nucleosomes, suggesting that PAD4's role is in chromatin decondensation rather than increasing histone-mediated killing. PAD4 is essential for histone citrullination and chromatin decondensation during NET formation. PAD4 knockout mice show reduced histone citrullination and NET formation. PAD4 is required for NET-mediated bacterial killing, as shown by experiments with S. flexneri and M1 GAS. PAD4-deficient neutrophils have reduced ability to kill bacteria, especially when NET formation is inhibited. The study highlights the importance of PAD4 in innate immunity and NET-mediated bacterial killing. PAD4 is a key factor in the formation of NETs and their antibacterial function. The results define a role for histone hypercitrullination in innate immunity during bacterial infection.