Mechanisms of iron acquisition and bacterial virulence

Martínez, José Luis; Delgado‐Iribarren, Alberto; Baquero, Fernando

doi:10.1111/j.1574-6968.1990.tb04085.x

Cited by 95 publications

(67 citation statements)

References 151 publications

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“…Excess iron increases the virulence of organisms as diverse as Escherichia (9), Klebsiella (10), Listeria (11), Neisseria (12), Pasteurella (11), Shigella (13), Salmonella (14,15), Vibrio (16), and Yersinia (17). Iron dextran injections in children, originally intended to prevent iron deficiencies, enhanced Escherichia coli bacteremia and meningitis (18).…”

Section: Iron: Can't Live With It Can't Live Without Itmentioning

confidence: 99%

Enterobactin: An archetype for microbial iron transport

Raymond

Dertz

Kim

2003

Proc. Natl. Acad. Sci. U.S.A.

792

692

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Bacteria have aggressive acquisition processes for iron, an essential nutrient. Siderophores are small iron chelators that facilitate cellular iron transport. The siderophore enterobactin is a triscatechol derivative of a cyclic triserine lactone. Studies of the chemistry, regulation, synthesis, recognition, and transport of enterobactin make it perhaps the best understood of the siderophore-mediated iron uptake systems, displaying a lot of function packed into this small molecule. However, recent surprises include the isolation of corynebactin, a closely related trithreonine triscatechol derivative lactone first found in Gram-positive bacteria, and the crystal structure of a ferric enterobactin complex of a protein identified as an antibacterial component of the human innate immune system.

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Section: Iron: Can't Live With It Can't Live Without Itmentioning

confidence: 99%

Enterobactin: An archetype for microbial iron transport

Raymond

Dertz

Kim

2003

Proc. Natl. Acad. Sci. U.S.A.

792

692

View full text Add to dashboard Cite

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“…In animal hosts, iron is usually bound to proteins such as transferrin and lactoferrin in extracellular fluid and to ferritin, hemoglobin, and heme-containing enzymes in cells (26,45). To utilize such complexes as iron sources, bacteria generally possess some sophisticated mechanisms, which include an iron uptake system mediated by high-affinity iron chelators called siderophores and a system for heme uptake via specific receptors (18,26,45).…”

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confidence: 99%

Impact of Siderophore Production on Pseudomonas aeruginosa Infections in Immunosuppressed Mice

Takase¹,

Nitanai²,

Hoshino³

et al. 2000

Infect Immun

247

278

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Pseudomonas aeruginosa produces siderophores, pyoverdin and pyochelin, for high-affinity iron uptake. To investigate their contribution to P. aeruginosa infections, we constructed allelic exchange mutants from strain PAO1 which were deficient in producing one or both of the siderophores. When inoculated into the calf muscles of immunosuppressed mice, pyochelin-deficient and pyoverdin-deficient mutants grew and killed the animals as efficiently as PAO1. In contrast, the pyochelin-and pyoverdin-deficient (double) mutant did not show lethal virulence, although it did infect the muscles. On the other hand, when inoculated intranasally, all mutants grew in the lungs and killed immunosuppressed mice. Compared with PAO1, however, the pyoverdin-deficient mutant and the double mutant grew poorly in the lungs, and the latter was significantly attenuated for virulence. Irrespective of the inoculation route, the pyoverdin-deficient and doubly deficient mutants detected in the blood were significantly less numerous than PAO1. Additionally, in vitro examination demonstrated that the growth of the double mutant was extremely reduced under a free-iron-restricted condition with apotransferrin but that the growth reduction was completely canceled by supplementation with hemoglobin as a heme source. These results suggest that both pyoverdin and pyochelin are required for efficient bacterial growth and full expression of virulence in P. aeruginosa infection, although pyoverdin may be comparatively more important for bacterial growth and dissemination. However, the siderophores were not always required for infection. It is possible that non-siderophore-mediated iron acquisition, such as via heme uptake, might also play an important role in P. aeruginosa infections.

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“…In animal hosts, iron is usually bound to proteins such as transferrin, lactoferrin, and ferritin and bound as heme to hemoglobin (Hb) and various enzymes (26,41). To utilize such complexes as iron sources, bacteria possess some sophisticated mechanisms, including an iron uptake system mediated by high-affinity iron chelators called siderophores and a heme uptake system, which involve specific receptors (21,26,41). In these systems of gram-negative bacteria, a cytoplasmic membrane protein known as TonB is generally accepted to play a crucial role.…”

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confidence: 99%

Requirement of the Pseudomonas aeruginosa tonB Gene for High-Affinity Iron Acquisition and Infection

Takase¹,

Nitanai²,

Hoshino³

et al. 2000

Infect Immun

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To investigate the contribution of the TonB protein to high-affinity iron acquisition in Pseudomonas aeruginosa, we constructed tonB-inactivated mutants from strain PAO1 and its derivative deficient in producing the siderophores pyoverdin and pyochelin. The tonB mutants could not grow in a free-iron-restricted medium prepared by apotransferrin addition, even though the medium was supplemented with each purified siderophore or with a heme source (hemoglobin or hemin). The tonB inactivation was shown to make P. aeruginosa unable to acquire iron from the transferrin with either siderophore. Introduction of a plasmid carrying the intact tonB gene restored growth of the tonB mutant of PAO1 in the free-iron-restricted medium without any supplements and restored growth of the tonB mutant of the siderophore-deficient derivative in the medium supplemented with pyoverdin, pyochelin, hemoglobin, or hemin. In addition, animal experiments showed that, in contrast to PAO1, the tonB mutant of PAO1 could not grow in vivo, such as in the muscles and lungs of immunosuppressed mice, and could not kill any of the animals. The in vivo growth ability and lethal virulence were also restored by introduction of the tonB-carrying plasmid in the tonB mutant. These results indicate clearly that the intact tonB gene-and, therefore, the TonB protein encoded by it-is essential for iron acquisition mediated by pyoverdin and pyochelin and via heme uptake in P. aeruginosa and suggest that the TonB-dependent iron acquisition may be essential for P. aeruginosa to infect the animal host.

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Mechanisms of iron acquisition and bacterial virulence

Cited by 95 publications

References 151 publications

Enterobactin: An archetype for microbial iron transport

Enterobactin: An archetype for microbial iron transport

Impact of Siderophore Production on Pseudomonas aeruginosa Infections in Immunosuppressed Mice

Requirement of the Pseudomonas aeruginosa tonB Gene for High-Affinity Iron Acquisition and Infection

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