cirA1 and cirA198 were the primary alleles in hypervirulent and multidrug-resistant K. pneumoniae lineages, respectively.
•CirA1 conferred K. pneumoniae with a higher iron transporting ability than CirA198.
•CirA1 was associated with increased cefiderocol susceptibility.
ABSTRACTCefiderocol 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 susceptibility.
KeywordsCefiderocol
Siderophore
Klebsiella pneumoniae
CirA
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