Proteomic and Transcriptomic Analyses Indicate Reduced Biofilm-Forming Abilities in Cefiderocol-Resistant Klebsiella pneumoniae

The advent of cefiderocol provides hope for the clinical treatment of multi-drug resistant gram-negative bacteria (GNB), especially those with carbapenem resistance. Resistance of Klebsiella pneumoniae to cefiderocol can be enhanced by acclimatization. In the present study, we collected cefiderocol resistant K. pneumoniae isolates during a 36-day acclimatization procedure while increasing the cefiderocol concentration in the culture medium. Strains were studied for changes in their biological characteristics using proteomics and transcriptomics. A decrease in biofilm formation ability was the main change observed among the induced isolates. Downregulation of genes involved in biofilm formation including hdeB, stpA, yhjQ, fba, bcsZ, uvrY, bcsE, bcsC, and ibpB were the main factors that reduced the biofilm formation ability. Moreover, downregulation of siderophore transporter proteins including the iron uptake system component efeO, the tonB-dependent receptor fecA, and ferric iron ABC transporter fbpA may be among the determining factors leading to cefiderocol resistance and promoting the reduction of biofilm formation ability of K. pneumoniae. This is the first study to investigate cefiderocol resistance based on comprehensive proteomic and transcriptomic analyses.