The perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve antiphage defense. However, the prevalence and effectiveness of minimal, single-component systems that cleave DNA remain unknown. Here, we describe a unique mode of nucleic acid immunity mediated by a single enzyme with nuclease and helicase activities, herein referred to as Nhi (nuclease-helicase immunity). This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi targets and degrades phage-specific replication intermediates. Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in antiphage defense.
The perpetual arms race between bacteria and their viruses (phages) has given rise to diverse immune systems, including restriction-modification and CRISPR-Cas, which sense and degrade phage-derived nucleic acids. These complex systems rely upon production and maintenance of multiple components to achieve antiphage defense. However, the prevalence and effectiveness of minimal, single-component systems that cleave DNA remain unknown. Here, we describe a unique mode of nucleic acid immunity mediated by a single enzyme with nuclease and helicase activities, herein referred to as Nhi (nuclease-helicase immunity). This enzyme provides robust protection against diverse staphylococcal phages and prevents phage DNA accumulation in cells stripped of all other known defenses. Our observations support a model in which Nhi targets and degrades phage-specific replication intermediates. Importantly, Nhi homologs are distributed in diverse bacteria and exhibit functional conservation, highlighting the versatility of such compact weapons as major players in antiphage defense.
Sensor:Unknown
Sensor:Phage protein sensing
Activator:Unknown
Activator:Direct binding
Effector:Nucleic acid degrading (?)
Effector:Nucleic acid degrading
PFAM:PF01443, PF09848, PF13604
PFAM:PF01443, PF09848, PF13604
contributors:
-Alba Herrero del Valle
relevantAbstracts:
-doi:10.1016/j.chom.2022.03.001
-doi:10.1016/j.chom.2022.09.017
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# Nhi
# Nhi
## Description
The Nhi (nuclease-helicase immunity) system targets and degrades specific phage DNA replication intermediates :ref{doi=10.1016/j.chom.2022.03.001}. Nayeemul Bari et al. showed that Nhi from *Staphylococcus epidermidis* protects against a diverse panel of staphylococcal phages and Millman et al. showed that a protein Nhi-like (that shares the domain organization with Nhi but not the sequence) from *Bacillus cereus* protects against some Bacillus phages :ref{doi=10.1016/j.chom.2022.03.001,10.1016/j.chom.2022.09.017}.
## Molecular mechanisms
Nhi contains two domains, a nuclease and a helicase domain that are both needed for the anti-phage activity. The nuclease domain has 3′–5′ exonuclease and plasmid nicking activities while the helicase unwinds dsDNA biderctionally. Nhi specifically recognizes phage single-stranded DNA binding proteins (SSB) that cover the phage genome to target this DNA for degradation thanks to its helicase and nuclease domains :ref{doi=10.1016/j.chom.2022.03.001}.
