Post-transfer instability limits zoonotic spread of IncI1-blaCTX-M-1 plasmids between chicken and human Escherichia coli

Plasmids are major vehicles for the dissemination of antimicrobial resistance genes across bacterial populations and hosts. Among Escherichia coli, IncI1 plasmids carrying the extended-spectrum ß-lactamase gene blaCTX-M-1 are frequent contributors to resistance in both poultry and human isolates. This study investigates the zoonotic dissemination potential of two IncI1-blaCTX-M-1 plasmids originating from chicken E. coli donors by comparing their conjugative transfer and post-transfer stability in panels of chicken and human E. coli recipients. Conjugation assays performed at 37 °C and 42 °C showed that transfer efficiency was mainly determined by recipient genotype rather than host origin or temperature. Genomic differences between donor and recipient strains, including the presence of large resident plasmids, influenced transfer success. In contrast, post-transfer maintenance proved to be strongly host-dependent, with plasmid loss rates approximately four-fold higher in human-derived transconjugants than in those from chickens. Instability in human recipients correlated with increased mutational load in the plasmidome and with distinct deletions arising in the transferred plasmids. These findings indicate that while prior exposure to related plasmids can mitigate initial fitness costs, it does not prevent long-term instability in new hosts. Consequently, the zoonotic dissemination of IncI1-blaCTX-M-1 plasmids may be constrained by host-specific post-transfer dynamics, underscoring the need for One Health risk assessments to integrate plasmid stability and evolutionary behavior across ecological boundaries.