The balance between defence systems and horizontal gene transfer shapes adaptation in clinical strains of Acinetobacter spp

Aims Bacteria experience various selective pressures from the environment, including exposure to antibiotics and bacteriophages, which shape their defence strategies and horizontal gene transfer (HGT) dynamics. The relationship between defence system repertoires and HGT in clinically relevant Acinetobacter species remains poorly understood, limiting our ability to predict resistance evolution and design targeted phage therapies. Methods and results We analysed 132 genomes from 18 Acinetobacter species, focusing on the interplay between defence architectures and HGT markers. Our results reveal that defence repertoires differed across lineages. Most Acinetobacter spp. harbour multiple defence systems, whereas the clinically dominant A. baumannii international clone 2 carried fewer but was strongly enriched for the phosphorothioation-based SspBCDE system and had very few restriction–modification systems. Strikingly, many defence systems were rarely found together. Defence genes were frequently associated with the presence of mobile elements, antibiotics, and heavy metal resistance. Plasmid-borne defence systems, especially BREX, were prevalent, highlighting the role of mobile elements in distributing both anti-phage defence and clinically relevant resistance traits. Conclusions Our results indicate that clinical success in A. baumannii is associated with a niche-driven defence profile and extensive linkage between defence genes, mobile elements, and resistance loci, which are likely to influence both HGT-mediated resistance acquisition and phage susceptibility.