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, $Ga^{3+}$ competes with $Fe^{3+}$ for binding to compounds that usually bind $Fe^{3+}$, thereby interfering with various essential biological reactions. In our present study, gallium(III) nitrate [$Ga(NO_3)_3$] could repress the growth of V. splendidus Vs without complete inhibition. In the presence of $Ga(NO_3)_3$, the secretion of homogentisic acid-melanin (HGA-melanin) in V. splendidus Vs cells could be increased by 4.8-fold, compared to that in the absence of $Ga(NO_3)_3$. HGA-melanin possessed the ability to reduce $Fe^{3+}$ to $Fe^{2+}$. 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 $640{\mu}M$ $Ga(NO_3)_3$, respectively. In conclusion, our study suggested that although $Ga(NO_3)_3$ could interfere with the growth of V. splendidus Vs, it could also stimulate both the production of $Fe^{3+}$-reducing HGA-melanin and the expression of feoA and feoB, which facilitate $Fe^{2+}$ transport in V. splendidus Vs.