A membrane-bound nuclease directly cleaves phage DNA during genome injection

Nature

by Daniel S. Saxton

February 26, 2026

AI-Generated Deep Dive Summary

Scientists have discovered a groundbreaking bacterial defense system called SNIPE (surface-associated nuclease inhibiting phage entry), which directly cleaves viral DNA during genome injection. Unlike traditional immune mechanisms like CRISPR-Cas or restriction-modification systems, SNIPE operates by localizing to the bacterial cell membrane and targeting phage DNA as it is injected into the host cell. This innovative defense mechanism provides a new strategy for distinguishing self from non-self in prokaryotes. The study revealed that SNIPE specifically cleaves phage DNA during the early stages of infection, effectively blocking phage λ and other siphoviruses from completing their genome entry. By associating with host proteins critical for phage genome injection, SNIPE exploits the spatial organization of this process to selectively target viral DNA. This mechanism is highly specific and avoids interfering with bacterial processes or plasmid transformation, making it a precise defense system. The findings highlight how bacteria have evolved sophisticated strategies to combat viral infections. By targeting the physical act of phage genome injection, SNIPE represents a previously unknown approach to directly neutralizing foreign genetic material. This discovery not only advances our understanding of prokaryotic immune systems but also opens new avenues for developing antiviral therapies inspired by bacterial defense mechanisms. The research underscores the importance of exploring alternative defense strategies beyond CRISPR and restriction systems. SNIPE’s unique mode of action—membrane-bound nuclease activity—demonstrates that bacteria possess diverse tools to combat viral infections, emphasizing the need to uncover more such systems in the future. This discovery could have implications for biotechnology and medicine, particularly in developing novel antiviral agents. Overall, SNIPE’s role as a widespread bacterial defense system challenges our understanding of immune strategies in prokaryotes. By directly targeting phage

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Originally published on Nature on 2/26/2026