Anti-defense systems on plasmids

Plasmids and other conjugative elements facilitate the horizontal transfer of genes encoding for various functions, including antibiotic resistance and virulence factors. In order to establish in recipient bacteria, the conjugative elements must overcome various defense mechanisms, such as CRISPR-Cas systems, restriction enzymes, and SOS response. Here, we demonstrate that an extensive repertoire of anti-defense genes is encoded on plasmids’ leading region, which is the first to transfer to recipient cells. This trait is universal across different conjugative elements and types of anti-defense genes. We show that the genes reside in an orientation and downstream to regulatory elements that could allow their early expression from single-stranded DNA. Our results could lead to the discovery of novel anti-defense systems among the numerous uncharacterized gene family encoded in the leading region. Further, they may help us understand key factors in the establishment of conjugative elements in recipient bacteria and the intricate co-evolution of defense and anti-defense systems.