Microorganisms 2026 Jul 10;147:. doi: 10.3390/microorganisms14071508.

The Vibrio splendidus Ferric Uptake Regulator Promotes Infection of Apostichopus japonicus Through Activation of the Type VI Secretion System.

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Iron is essential for bacterial survival and pathogenicity. During infection, bacteria face iron limitation imposed by the host and must develop strategies to obtain iron and maintain virulence. The ferric uptake regulator (Fur) is a major iron-responsive regulator that coordinates iron metabolism and virulence-related functions in many bacteria. However, whether and how Fur regulates virulence systems in the Apostichopus japonicus pathogen Vibrio splendidus remains unclear. In this study, the VsFur-knockdown strain was used to investigate the role of VsFur in T6SS regulation and virulence-associated traits. Aggregation and adhesion assays showed that knockdown of VsFur reduced bacterial aggregation and adhesion to coelomocytes of the A. japonicus. qPCR and Western blot analyses revealed that iron limitation and VsFur knockdown both significantly inhibited the expression of T6SS-related genes and the secretion of Hcp. In terms of mechanism, VsFur directly bound to the promoter region of the T6SS gene cluster and positively regulated its transcription. ELISA and immunofluorescence analyses further showed that knockdown of VsFur significantly reduced the secretion and host-cell delivery of the T6SS effector proteins Hcp and VgrG. Moreover, hemolysis and siderophore production assays showed that VsFur knockdown enhanced hemolytic activity and siderophore production, suggesting the existence of a compensatory mechanism. Collectively, these results reveal a novel regulatory relationship between VsFur and virulence in V. splendidus, providing new insights into iron-dependent virulence regulation and a theoretical basis for the development of novel strategies for the prevention of bacterial diseases in A. japonicus aquaculture.

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