IncFIB/FII conjugative iuc3-carrying virulence plasmids of clinical hypervirulent Klebsiella pneumoniae are multi-drug resistant.

Aerobactin encoding loci is the key virulence factor in the virulence plasmid of Klebsiella pneumoniae (Kp). The iuc1 and iuc2 loci are most commonly detected and well-studied, while the iuc3 lineage is less understood. The study investigated comprehensively the iuc3-carrying plasmids in Kp strains providing insights into the diversity, transmission potential and contribution to Kp virulence. The iuc3 was encoded on plasmids ranging from 177,328 bp to 249,880 bp, primarily of the IncFIB/FII type, often carrying multi-drug resistance (MDR) regions. Conjugation experiments demonstrated the transferability of iuc3-carrying plasmids, conferring additional resistance to recipient strains. Siderophore production assays indicated that the iuc3 gene cluster significantly enhanced iron acquisition in transconjugants. Analysis of 69,969 Kp isolates from the NCBI Pathogen Detection database identified 872 iuc3-carrying strains across 205 STs and 69 KLs, indicating widespread genetic diversity. These strains were increasingly detected in human clinical samples over time, with additional reservoirs in animals, food, and the environment. The findings underscore the public health threat posed by iuc3-carrying Kp strains, emphasizing the need for surveillance and control measures to prevent the spread of MDR-HvKp clones. This study highlights the complex interplay between plasmid-mediated resistance, virulence, and the potential for horizontal gene transfer in Klebsiella spp.