<i>In Vitro</i> Evolution of Cefiderocol Resistance in an NDM-Producing Klebsiella pneumoniae Due to Functional Loss of CirA
Christi L. McElheny, Erin L. Fowler, Alina Iovleva, Ryan K. Shields, Yohei Doi
Abstract
Cefiderocol, a newly approved cephalosporin agent with an extensive spectrum of activity against Gram-negative bacteria, is a siderophore cephalosporin that utilizes iron transporters to access the bacterial periplasm. Loss of functional CirA, an iron transporter, has been associated with cefiderocol resistance. Here, we show that such genetic change can be selected under selective pressure and cause high-level cefiderocol resistance, but with a high fitness cost. Whether these resistant mutants can survive beyond selective pressure will inform stewardship of this agent in the clinic.
Topics & Concepts
Klebsiella pneumoniaeSiderophoreBiologyComplementationMutantCephalosporinMicrobiologyGeneticsGeneStrain (injury)Pseudomonas aeruginosaKlebsiellaAdaptation (eye)MutationEnterobacteriaceaeBacteriaATP-binding cassette transporterExperimental evolutionAntimicrobialInsertion sequenceTransporterComputational biologyAntibiotic Resistance in BacteriaBacterial Genetics and BiotechnologyBacterial biofilms and quorum sensing