Randomized trial investigates cefiderocol resistance mechanisms in Enterobacter hormaechei, indicating mutation's role in resistance development.
Key Points
To investigate cefiderocol resistance in clinical Enterobacter hormaechei isolates and genetic mechanisms involved, focusing on the TonB-dependent receptor mutations.
Exposed clinical E. hormaechei isolates to increasing cefiderocol concentrations using disk diffusion and broth microdilution.
Performed whole genome sequencing to identify resistance mutations.
Used CRISPR-Cas9 for site-directed mutagenesis to confirm causality.
Six spontaneous mutants exhibited FDC MICs from 2 to 16 mg/L.
All mutants had mutations in the tonB-dependent receptor gene such as frameshift mutations and premature stop codons.
CRISPR-engineered strains with identical mutations showed the same resistance phenotype, verifying the mechanism.