Acinetobacter baumannii is an important nosocomial pathogen. Mechanisms that allow A. baumannii to cause human infection are still poorly understood. Iron is an essential nutrient for bacterial growth in vivo, and the multiplicity of iron-uptake systems in A. baumannii suggests that iron acquisition contributes to the ability of A. baumannii 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 A. baumannii genome invariably contains three tonB genes (tonB1, tonB2 and tonB3), whose role in iron-uptake is poorly understood. Here, we generated A. baumannii knock-out mutants in feo and/or tonB genes. We report that tonB3 is essential for A. baumannii growth under iron limiting conditions, whereas tonB1, tonB2 and feoB appear dispensable for ferric iron-uptake. tonB3 deletion resulted in reduced intracellular iron content despite siderophore over-production, supporting a key role of TonB3 in iron-uptake. Different from tonB1 and tonB2, the promoters of tonB3 and feo contain functional Fur boxes and are up-regulated 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 A. baumannii pathogenicity. Hence, TonB3 represents a promising target for novel anti-bacterial therapies and for the generation of attenuated vaccine strains.

Runci, F., Gentile, V., Frangipani, E., Rampioni, G., Leoni, L., Lucidi, M., et al. (2019). The contribution of active iron-uptake to Acinetobacter baumannii pathogenicity. INFECTION AND IMMUNITY [10.1128/IAI.00755-18].

The contribution of active iron-uptake to Acinetobacter baumannii pathogenicity

Runci, Federica;Gentile, Valentina;Frangipani, Emanuela;Rampioni, Giordano;Leoni, Livia;Lucidi, Massimiliano;Visaggio, Daniela;Visca, Paolo
2019

Abstract

Acinetobacter baumannii is an important nosocomial pathogen. Mechanisms that allow A. baumannii to cause human infection are still poorly understood. Iron is an essential nutrient for bacterial growth in vivo, and the multiplicity of iron-uptake systems in A. baumannii suggests that iron acquisition contributes to the ability of A. baumannii 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 A. baumannii genome invariably contains three tonB genes (tonB1, tonB2 and tonB3), whose role in iron-uptake is poorly understood. Here, we generated A. baumannii knock-out mutants in feo and/or tonB genes. We report that tonB3 is essential for A. baumannii growth under iron limiting conditions, whereas tonB1, tonB2 and feoB appear dispensable for ferric iron-uptake. tonB3 deletion resulted in reduced intracellular iron content despite siderophore over-production, supporting a key role of TonB3 in iron-uptake. Different from tonB1 and tonB2, the promoters of tonB3 and feo contain functional Fur boxes and are up-regulated 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 A. baumannii pathogenicity. Hence, TonB3 represents a promising target for novel anti-bacterial therapies and for the generation of attenuated vaccine strains.
Runci, F., Gentile, V., Frangipani, E., Rampioni, G., Leoni, L., Lucidi, M., et al. (2019). The contribution of active iron-uptake to Acinetobacter baumannii pathogenicity. INFECTION AND IMMUNITY [10.1128/IAI.00755-18].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/345580
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