Catecholate siderophore receptor CirA impacts cefiderocol susceptibility in Klebsiella pneumoniae

ElsevierVolume 60, Issue 4, October 2022, 106646International Journal of Antimicrobial AgentsHighlights•

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.

ABSTRACT

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 susceptibility.

Keywords

Cefiderocol

Siderophore

Klebsiella pneumoniae

CirA

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