Association of cirA allelic variation with cefiderocol susceptibility and virulence-associated lineages in Klebsiella pneumoniae.

Abstract

Background: Klebsiella pneumoniae comprises multidrug-resistant and hypervirulent lineages, and cefiderocol uptake may partly depend on iron transport receptors such as CirA. However, the clinical distribution and phenotypic relevance of cirA alleles remain unclear.

Objectives: To determine whether cirA allelic variation is associated with cefiderocol susceptibility and virulence-related traits in clinical K. pneumoniae isolates.

Methods: We analysed 480 non-duplicate clinical isolates for cirA allele, sequence type, capsular locus, β-lactamase genes, cefiderocol MICs by broth microdilution in iron-depleted cation-adjusted Mueller-Hinton broth, siderophore production, virulence score and Galleria mellonella lethality.

Results: Five major cirA allelic groups were identified. cirA198 was associated with higher cefiderocol MIC distributions and included all cefiderocol-resistant isolates, which also carried bla_KPC, bla_NDM and bla_SHV, indicating multifactorial reduced susceptibility. In contrast, cirA1 was linked to ST23-KL1 isolates and was associated with higher virulence scores, increased siderophore production and greater lethality in G. mellonella.

Conclusions: Major cirA alleles are associated with distinct K. pneumoniae clonal backgrounds: cirA198 with ST11-KL64 multidrug-resistant isolates and elevated cefiderocol MICs, and cirA1 with ST23-KL1 hypervirulence-associated traits. cirA allelic typing may serve as a lineage-associated marker, although isogenic studies are needed to define independent causal roles.