Strategies for zygotic gene expression during plasmid establishment

Conjugative plasmids are key drivers of horizontal gene transfer and the spread of antimicrobial resistance. Their successful establishment in new hosts requires overcoming diverse bacterial defence mechanisms, such as restriction-modification systems, CRISPR-Cas systems, and the SOS response. Plasmids achieve this through a leading region-encoded zygotic program of anti-defence genes expressed early in conjugation. This program employs diverse strategies, including single-stranded promoters, repressed double-stranded promoters, and protein translocation. This review explores the diversity of these zygotic programs, the mechanisms underlying their timely regulation, and the array of anti-defence functions they encode. Further investigation of leading region genes is crucial for discovering novel counter-defence strategies and understanding their tailored regulation across diverse plasmid and bacterial species, ultimately enabling us to better understand and potentially manipulate plasmid transfer. • Successful plasmid conjugation requires overcoming diverse host defence mechanisms. • The plasmid leading region encodes a zygotic program expressed early in conjugation. • Zygotic induction is achieved through ssDNA promoters or repressed dsDNA promoters. • Leading region anti-defence genes counteract diverse defences, including R-M, SOS response, and CRISPR-Cas.