Abundant bacterial nucleoid-associated protein H-NS limits plasmid transfer through mechanical modification of DNA

The ongoing arms race between prokaryotes and mobile genetic elements (MGEs) gives rise to a myriad of host-defense systems that detect and degrade invading nucleic acids. However, it is yet unclear whether changing the mechanical properties of nucleic acids can impact plasmid/phage invasion. Here, we demonstrate that H-NS, an abundant nucleoid-associated protein (NAP), limits plasmid transfer by directly binding to and oligomerizing along with transforming double-stranded DNA. The constitutive defense function of H-NS can be complemented by convergently evolved NAPs from different phyla. H-NS proteins form intramolecular bridges between DNA duplexes within incoming plasmids. Different from other defense systems that exist at low levels prior to detecting MGEs, major NAPs exist in high abundance, which may moonlight as a constant plasmid surveillance agent. Our study implies that mechanical modification of nucleic acids may be an underexplored mechanism for prokaryotic immunity, which could help balance the advantages and disadvantages of MGEs.