AUTHOR=Bao Jinfeng , Xie Lu , Ma Yating , An Ran , Gu Bing , Wang Chengbin 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.778190

DOI=10.3389/fmicb.2021.778190

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Klebsiella pneumoniae</italic> to cefiderocol can be enhanced by acclimatization. In the present study, we collected cefiderocol resistant <italic>K. pneumoniae</italic> 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 <italic>hdeB, stpA, yhjQ, fba, bcsZ, uvrY, bcsE, bcsC</italic>, and <italic>ibpB</italic> were the main factors that reduced the biofilm formation ability. Moreover, downregulation of siderophore transporter proteins including the iron uptake system component <italic>efeO</italic>, the tonB-dependent receptor <italic>fecA</italic>, and ferric iron ABC transporter <italic>fbpA</italic> may be among the determining factors leading to cefiderocol resistance and promoting the reduction of biofilm formation ability of <italic>K. pneumoniae</italic>. This is the first study to investigate cefiderocol resistance based on comprehensive proteomic and transcriptomic analyses.</p>