Aerobactin-Mediated Iron Acquisition Enhances Biofilm Formation, Oxidative Stress Resistance, and Virulence of Yersinia pseudotuberculosis

Abstract

Aerobactin is a citrate-hydroxamate siderophore that is critical for the virulence of pathogenic enteric bacteria. However, although the aerobactin-producing <i>iucABCD</i>-<i>iutA</i> operon is distributed widely in the genomes of <i>Yersinia</i> species, none of the pathogenic <i>Yersinia</i> spp. was found to produce aerobactin. Here, we showed that the <i>iucABCD</i>-<i>iutA</i> operon in the food-borne enteric pathogen <i>Yersinia pseudotuberculosis</i> YPIII is a functional siderophore system involved in iron acquisition. The expression of the operon was found to be directly repressed by the ferric uptake regulator (Fur) in an iron concentration-dependent manner. In addition, we demonstrated that the aerobactin-mediated iron acquisition contributes to bacterial growth under iron-limited conditions. Moreover, we provided evidence that aerobactin plays important roles in biofilm formation, resistance to oxidative stress, ROS removal, and virulence of <i>Y. pseudotuberculosis</i>. Overall, our study not only uncovered a novel strategy of iron acquisition in <i>Y. pseudotuberculosis</i> but also highlighted the importance of aerobactin in the pathogenesis of <i>Y. pseudotuberculosis</i>.