Comprehensive analysis of Enterobacteriaceae IncX plasmids reveals robust conjugation regulators PrfaH, H-NS, and conjugation-fitness tradeoff.

ABSTRACT: Conjugative IncX plasmids are vital for spreading clinically significant antibiotic resistance genes. We identified key factors governing the conjugative process of IncX plasmids, the plasmid encoded activator PrfaH and inhibitor H-NS. Deletion of prfaH completely abolishes conjugative transfer, and the PrfaH binding site is an ops-like sequence located downstream of the prfaH promoter. We solved the crystal structure of PrfaH and identified the residues that likely mediate interactions with its target. The IncX3 plasmid-encoded H-NS inhibits conjugation by directly repressing PrfaH expression, while simultaneously enhancing host fitness. This tradeoff between plasmid conjugation and fitness is indispensable for plasmid persistence in nutrient-deprived environments. The presence of PrfaH p

SUBMITTER: Yang J 

PROVIDER: S-EPMC11880322 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature