Antimicrobial Resistance and Genomic Characteristics of ESBL-Producing Proteus mirabilis from Farmed Mink in Shandong Province, China.

Background/Objectives: Proteus mirabilis is an opportunistic pathogen and a potential reservoir of clinically important antimicrobial resistance genes in animal production. However, mink-derived P. mirabilis remains poorly characterized. This study investigated multidrug-resistant and extended-spectrum β-lactamase (ESBL)-producing isolates from intensive mink farms, focusing on clinically important β-lactamase genes, their genomic backgrounds, and mobile genetic elements (MGEs). Methods: Among 373 fecal and intestinal-content samples collected from six mink farms in Shandong Province, China, 68 P. mirabilis isolates were recovered. All underwent antimicrobial susceptibility testing, ESBL confirmation, and virulence-associated phenotypic assays. The 39 ESBL-positive isolates underwent whole-genome sequencing, followed by analyses of antimicrobial resistance genes, the pangenome, and MGEs and comparison with 198 publicly available genomes. Results: Of the 373 sampled mink, 68 (18.2%) were P. mirabilis positive, and 39 (10.5%) carried ESBL-producing isolates. Of the 68 isolates, 63 (92.6%) were multidrug resistant, and 39 (57.4%) were ESBL positive. All exhibited strong biofilm formation and urease activity, while 83.8% showed strong swarming motility. Among the sequenced isolates, blaCTX-M genes were identified in 32 isolates and blaNDM-1 in three. Both blaCTX-M-65- and blaNDM-1-positive isolates were distributed across multiple genomic lineages, with blaCTX-M-65 additionally detected in multiple sequence types. This distribution indicates that these genes were not restricted to a single clone but does not demonstrate horizontal gene transfer. MGE-associated features showed same-contig co-occurrence with several resistance genes, notably IS903-blaCTX-M-65 and ISAba125-blaNDM-1. The sequenced isolates also exhibited substantial accessory-genome diversity and widely distributed virulence determinants associated with adhesion, motility, iron acquisition, and toxin-related functions. Conclusions: Mink-derived P. mirabilis exhibited extensive multidrug resistance and carried clinically important β-lactamase genes across diverse genomic backgrounds. These findings support the inclusion of fur-animal production systems in One Health surveillance of antimicrobial-resistant P. mirabilis.