Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP

ST15 has become one of the most common sequence types of carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) in China; however, the characteristics of ST15 CRKP remains elusive. This study included a total of 72 unique CRKP isolates, comprising ST15, ST11, ST307, and ST2237, collected from an intensive care unit between 2019 and 2022 to investigate the clinical and biological characteristics as well as the virulence of ST15 CRKP. Whole genome sequencing for 72 CRKP strains and transcriptome sequencing of ST11 and ST15 CRKP after serum exposure was also performed. The virulence of ST15 was similar to that of ST11-KL47, which carries the <i>rmpA2</i> and aerobactin virulence genes, and higher than that of ST11-KL10 and ST307. This may be attributed to its serum resistance. Whole-genome sequencing revealed that genes related to iron uptake (<i>sitA/C/D</i>), the type VI secretion system, and adherence were associated with the serum resistance of ST15. Furthermore, transcriptomic analysis showed that ST15 CRKP strains upregulated genes associated with iron transport and metabolism upon serum exposure. The effect of iron on serum resistance in ST15 was confirmed by supplementing with FeSO₄ and FeCl₃. Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP, with <i>sitA/C/D</i> potentially serving as key virulence genes.