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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.

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