Contribution of Active Iron Uptake to Acinetobacter baumannii Pathogenicity.

is an important nosocomial pathogen. Mechanisms that allow to cause human infection are still poorly understood. Iron is an essential nutrient for bacterial growth , and the multiplicity of iron uptake systems in suggests that iron acquisition contributes to the ability of to cause infection. In Gram-negative bacteria, active transport of ferrisiderophores and heme relies on the conserved TonB-ExbB-ExbD energy-transducing complex, while active uptake of ferrous iron is mediated by the Feo system. The genome invariably contains three genes (, , and ), whose role in iron uptake is poorly understood. Here, we generated mutants with knockout mutations in the and/or gene. We report that is essential for growth under iron-limiting conditions, whereas , , and appear to be dispensable for ferric iron uptake. deletion resulted in reduced intracellular iron content despite siderophore overproduction, supporting a key role of TonB3 in iron uptake. In contrast to the case for and , the promoters of and contain functional Fur boxes and are upregulated in iron-poor media. Both TonB3 and Feo systems are required for growth in complement-free human serum and contribute to resistance to the bactericidal activity of normal human serum, but only TonB3 appears to be essential for virulence in insect and mouse models of infection. Our findings highlight a central role of the TonB3 system for pathogenicity. Hence, TonB3 represents a promising target for novel antibacterial therapies and for the generation of attenuated vaccine strains.