Catecholate siderophore receptor CirA impacts cefiderocol susceptibility in Klebsiella pneumoniae

Cefiderocol is a cephalosporin antibiotic presenting expanded antimicrobial activity. CirA is a gateway for cefiderocol to enter bacterial cells. We found that cirA1 and cirA198 were primary alleles in Klebsiella pneumoniae. CirA1 exhibited higher iron-transporting ability than CirA198 in iron-limited conditions. The cefiderocol minimum inhibitory concentration (MIC) increased from 0.5 mg/L to 2 mg/L when cirA1 was mutated to cirA198. Consistently, the MIC showed a 4-fold decrease when cirA198 was mutated to cirA1. Therefore, CirA1 has higher capacity to transport siderophores, contributing to increased cefiderocol sus-ceptibility. (c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

Cefiderocol, a cephalosporin antibiotic, exhibits expanded antimicrobial activity. CirA1 has higher iron-transporting ability than CirA198, leading to increased susceptibility to Cefiderocol.