Host genetics regulate bacterial plasmid conjugation differentially in avian ceca explant co-culture through secretory miRNA

The rapid emergence of multidrug-resistant virulent bacteria poses a global health concern. It is enabled through the lateral transfer of plasmid-carrying antibiotic resistance and virulence genes between bacteria. The guts of animals, particularly chickens, are recognized as reservoirs for this plasmid transfer, yet the regulation of this process by host factors remains poorly understood. Here, we examined the role of chicken intestinal tissue in the lateral transfer of the antimicrobial resistance plasmid pAPEC-O2-211A-ColV from its natural bacterial host, E. coli APEC-O2-211, to the plasmid-free E. coli HS-4 using an explant model, and how chicken host miRNAs contribute to this process. Ceca tissues collected from commercial and heritage birds were exposed to bacterial conjugation mixtures. Host small RNAs were extracted from chicken ceca tissue and evaluated for their effect on conjugation in vitro. We observed the expected bactericidal effect of chicken host tissues on both donor and recipient populations, alongside a variable response of bacterial conjugation influenced by different host genetic backgrounds. Additionally, we observed a correlation between small RNAs, mimic RNAs and bacterial plasmid conjugation in vitro. This study shed light on the role of small RNAs derived from host tissue in the differential regulation of bacterial plasmid conjugation.