Horizontal gene transfer facilitates the dissemination of blaCTX-M and blaNDM in Escherichia coli isolates from humans and pigs in Sichuan Province, China

The transmission of pathogenic bacteria and antimicrobial resistance genes (ARGs) between humans and livestock poses a critical public health challenge within the “One Health” framework. Here, we investigated the transmission dynamics and genomic characteristics of bla CTX-M- and bla NDM- positive Escherichia coli strains isolated from farm workers and pigs. From 1,001 fecal samples collected in Sichuan Province, China (2023), 110 E. coli isolates carrying bla CTX-M and/or bla NDM were recovered and assigned to 42 distinct sequence types (STs). Phylogenetic analysis revealed 10 intraherd transmission events; no direct evidence of cross-species transmission between humans and pigs was observed. Whole-genome sequencing revealed nine bla CTX-M variants and three bla NDM variants. Analysis of statistical correlations and genetic environments revealed distinct mobilization mechanisms: the dissemination of bla CTX-M was primarily mediated by IS 903B , IS Ec9 , and IS 26 , whereas bla NDM was structurally associated with IS 3000 and IS 26 , which were harbored by diverse plasmids, including IncFIB, IncY, IncHI2, and IncX3. Notably, conjugation experiments demonstrated the transferability of IncHI2 and IncX3 plasmids. The high similarity of genetic environments flanking resistance genes in human- and swine-derived isolates suggests that mobile genetic elements play a pivotal role in the horizontal transfer of these resistance determinants. Collectively, our findings indicate that the dissemination of bla CTX-M and bla NDM at the human–animal interface is driven primarily by horizontal gene transfer (HGT) rather than clonal expansion.