Gallium(III) Nitrate Inhibits Pathogenic Vibrio splendidus Vs by Interfering with the Iron Uptake Pathway

It is well known that iron is critical for bacterial growth and pathogenic virulence. Due to chemical similarity, Ga³⁺ competes with Fe³⁺ for binding to compounds that usually bind Fe³⁺, thereby interfering with various essential biological reactions. In our present study, gallium(III) nitrate [Ga(NO₃)₃] could repress the growth of V. splendidus Vs without complete inhibition. In the presence of Ga(NO₃)₃, the secretion of homogentisic acid-melanin (HGAmelanin) in V. splendidus Vs cells could be increased by 4.8-fold, compared to that in the absence of Ga(NO₃)₃. HGA-melanin possessed the ability to reduce Fe³⁺ to Fe²⁺. In addition, HGA-melanin increased the mRNA levels of feoA and feoB, genes coding Fe²⁺ transport system proteins to 1.86- and 6.1-fold, respectively, and promoted bacterial growth to 139.2%. Similarly, the mRNA expression of feoA and feoB was upregulated 4.11-fold and 2.71-fold in the presence of 640 μM Ga(NO₃)₃, respectively. In conclusion, our study suggested that although Ga(NO₃)₃ could interfere with the growth of V. splendidus Vs, it could also stimulate both the production of Fe³⁺-reducing HGA-melanin and the expression of feoA and feoB , which facilitate Fe²⁺ transport in V. splendidus Vs.