DNA mimicking ArdA anti-restriction proteins specifically inhibit restriction (endonuclease) activity of the type I restriction-modification (RM) system. An ArdA monomer is comprised of three α-β domains (the N-domain, Central domain, and C-domain), each with a different fold. Here we describe an alignment of the amino acid (a.a.) sequences of the ArdA with a conserved 20-a.a. motif in the N domain. The N domains of ArdA proteins of the Gram-positive bacteria Arthrobacter sp. and Bifidobacterium longum, and the Gram-negative bacteria Pseudomonas plecoglossicida are capable of inhibiting the repressive activity of the H-NS global silencer protein in Escherichia coli cells. The presence of the H-NS inhibiting N domain in the ArdA structure enables horizontal gene transfer by mobile elements, including conjugative plasmids and transposons. Specifically, it aids in overcoming intercellular restriction barriers, allowing faster adaption to the genome context of the recipient bacterium.