Analysis of P-type type IV secretion system-encoding plasmid diversity uncovers extensive secretion system conservation and diverse antibiotic resistance determinants.

is globally recognized as a multi-drug-resistant pathogen of critical concern due to its capacity for horizontal gene transfer and resistance to antibiotics. Phylogenetically diverse species mediate human infection, including many considered as important emerging pathogens. While globally recognized as a pathogen of concern, pathogenesis mechanisms are poorly understood. P-type type IV secretion systems (T4SSs) represent important drivers of pathogen evolution, responsible for horizontal gene transfer and secretion of proteins that mediate host-pathogen interactions, contributing to pathogen survival, antibiotic resistance, virulence, and biofilm formation. Genes encoding a P-type T4SS were previously identified on plasmids harboring the carbapenemase gene in several clinically problematic ; however, their prevalence among the genus, geographical distribution, the conservation of T4SS proteins, and full capacity for resistance genes remain unclear. Using systematic analyses, we show that these plasmids belong to a group of 53 P-type T4SS-encoding plasmids in 20 established species, the majority of clinical relevance, including diverse sequence types and one strain of . The strains were globally distributed in 14 countries spanning five continents, and the conjugative operon's T4SS proteins were highly conserved in most plasmids. A high proportion of plasmids harbored resistance genes, with 17 different genes spanning seven drug classes. Collectively, this demonstrates that P-type T4SS-encoding plasmids are more widespread among the genus than previously anticipated, including strains of both clinical and environmental importance. This research provides insight into the spread of resistance genes among and highlights a group of plasmids of importance for future surveillance.