Comparative analysis of early immune responses in zebrafish infected with carbapenem-resistant and carbapenem-susceptible Klebsiella pneumoniae strains

作者：Yi Y, Liu J, Yang X, Wu G · 发表于：Fish & shellfish immunology · 年份：2026 · DOI：10.1016/j.fsi.2026.111533 · 研究领域：Zebrafish、Klebsiella pneumoniae、Klebsiella Infections、Immunity, Innate、Carbapenems、Fish Diseases、Animals、Anti-Bacterial Agents、Carbapenem-Resistant Enterobacteriaceae

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a critical public health threat with limited treatment options and high mortality, yet its immune evasion strategies remain poorly understood compared to carbapenem-susceptible strains (CSKP). Using a zebrafish infection model, we demonstrate that the tested ST258 CRKP strain employs a dual strategy of hematopoietic disruption and broad immune suppression to evade host defenses. In this comparison, both the ST258 CRKP and the ST86 CSKP strains initially suppressed kidney hematopoietic precursors, but only the ST86 CSKP permitted complete cellular recovery by 48 h post-infection (hpi), revealing ST258 CRKP's persistent impairment of hematopoiesis. Functionally, the ST258 CRKP caused prolonged locomotor deficits and significantly weaker early neutrophil/macrophage responses compared to the ST86 CSKP. Transcriptomic profiling uncovered fundamentally different immune activation patterns: while the ST86 CSKP induced robust, coordinated activation of NOD-like receptor (NLR), Toll-like receptor (TLR), and C-type lectin receptor (CLR) pathways, the CRKP strain selectively activated NLR signaling while actively suppressing complement/coagulation cascades, TLR, and RIG-I-like receptor (RLR) pathways. These findings reveal that ST258 CRKP's enhanced pathogenicity stems from combined hematopoietic suppression and broad-spectrum immune pathway inhibition, providing new insights for host-directed therapies against this antimicrobial r...