Amonabactin Synthetase G Regulates Aeromonas hydrophila Pathogenicity Through Modulation of Host Wnt/β-catenin...

Aeromonas hydrophila is a significant opportunistic pathogen with a broad host range. It produces a catecholate siderophore, amonabactin, during iron starvation, but the in vivo infection mechanism that involves amonabactin is unclear. This study aims to elucidate the role of amonabactin synthetase G (AmoG) in the pathogenicity of A. hydrophila and its impact on gut barrier function.

ΔAmoG was generated by deleting the AMP-binding domain of AmoG in A. hydrophila CCL1. In vivo infection experiments were conducted to assess the mutant's iron-chelating ability and pathogenicity. Complementation of ΔAmoG with AmoG (ΔAmoG-C) was performed to confirm the observed phenotypes. Transcriptomic and qRT-PCR analyses were used to investigate gene expression changes in infected fish. Goblet cell counts, tight junction expression, and D-lactic acid and LPS levels were measured to evaluate gut barrier function.

ΔAmoG exhibited impaired iron-chelating ability and reduced pathogenicity compared to wild-type CCL1. Complementation with AmoG restored virulence in ΔAmoG-C. Transcriptomic and qRT-PCR analyses revealed an elevated expression of Wnt/β-catenin pathway components and antimicrobial genes in ΔAmoG-infected fish. Further investigation indicated increased goblet cells and an enhanced expression of tight junctions, as well as lower D-lactic acid and LPS levels, in ΔAmoG-infected fish. However, gut permeability, bacterial load, and lethality did not significantly differ between CCL1, ΔAmoG, and ΔAmoG-C infections when the Wnt/β-catenin pathway was activated.

AmoG plays a crucial role in A. hydrophila pathogenicity by modulating host Wnt/β-catenin signaling and gut mucosal barrier function. This study provides insights into the pathogenesis of A. hydrophila and potential therapeutic targets.