Genomic analysis of IncH plasmids reveals their role as drivers of antimicrobial resistance and adaptive traits in enterobacterales

Plasmids of the incompatibility group H (IncH) are large mobile elements that confer multidrug resistance and are prevalent in Enterobacterales from clinical and environmental sources. We analyzed 1308 globally distributed IncH plasmid sequences to assess their genomic features and functional potential. IncH plasmids were classified into IncHI1 and IncHI2, with IncHI1 subdivided into IncHI1B and IncHI1AB based on co-occurring replication proteins. These subtypes exhibited distinct host preferences and genomic patterns. IncH plasmids carried antimicrobial resistance genes and other adaptive determinants at comparable frequencies across environments. They encoded multiple replication and relaxase proteins, supporting broad host range and plasmid exclusion. Core genes included the Hha regulator, involved in virulence and conjugation; a DNA (cytosine-5)-methyltransferase contributing to AT-rich content; Cobamide synthase, potentially linked to metal tolerance; and the ter operon, associated with tellurium resistance and stress adaptation. Integron-associated genes such as qacEΔ1, sul1, and blaIMP promoted resistance to quaternary ammonium compounds, sulfonamides, and carbapenems. Notably, ~60% of nonredundant IncH plasmids encoded sulfonamide, quaternary ammonium compound, and β-lactam resistance, while over 70% harbored aminoglycoside resistance genes. These findings highlight IncH plasmids as reservoirs of clinically relevant genes and stress-response functions, reinforcing their importance for monitoring antibiotic resistance dissemination and environmental adaptability within Enterobacterales.