A unique mode of nucleic acid immunity performed by a multifunctional bacterial enzyme

S. M.Nayeemul Bari, Lucy Chou-Zheng, Olivia Howell, Motaher Hossain, Courtney M. Hill, Tori A. Boyle, Katie Cater, Vidya Sree Dandu, Alexander Thomas, Barbaros Aslan, Asma Hatoum-Aslan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)570-582.e7
JournalCell Host and Microbe
Issue number4
StatePublished - Apr 13 2022


  • Staphylococcus
  • antiphage defense
  • bacterial innate immunity
  • bacteriophage restriction

ASJC Scopus subject areas

  • Virology
  • Parasitology
  • Microbiology


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