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  • Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae.

Aerobactin mediates virulence and accounts for increased siderophore production under iron-limiting conditions by hypervirulent (hypermucoviscous) Klebsiella pneumoniae.

Infection and immunity (2014-03-26)
Thomas A Russo, Ruth Olson, Ulrike Macdonald, Daniel Metzger, Lauren M Maltese, Eric J Drake, Andrew M Gulick
PMID24664504
ABSTRACT

Hypervirulent (hypermucoviscous) Klebsiella pneumoniae (hvKP) strains are an emerging variant of "classical" K. pneumoniae (cKP) that cause organ and life-threatening infection in healthy individuals. An understanding of hvKP-specific virulence mechanisms that enabled evolution from cKP is limited. Observations by our group and previously published molecular epidemiologic data led us to hypothesize that hvKP strains produced more siderophores than cKP strains and that this trait enhanced hvKP virulence. Quantitative analysis of 12 hvKP strains in iron-poor minimal medium or human ascites fluid showed a significant and distinguishing 6- to 10-fold increase in siderophore production compared to that for 14 cKP strains. Surprisingly, high-pressure liquid chromatography (HPLC)-mass spectrometry and characterization of the hvKP strains hvKP1, A1142, and A1365 and their isogenic aerobactin-deficient (ΔiucA) derivatives established that aerobactin accounted for the overwhelming majority of increased siderophore production and that this was not due to gene copy number. Further, aerobactin was the primary factor in conditioned medium that enhanced the growth/survival of hvKP1 in human ascites fluid. Importantly the ex vivo growth/survival of hvKP1 ΔiucA was significantly less than that of hvKP1 in human ascites fluid, and the survival of outbred CD1 mice challenged subcutaneously or intraperitoneally with hvKP1 was significantly less than that of mice challenged with hvKP1 ΔiucA. The lowest subcutaneous and intraperitoneal challenge inocula of 3 × 10(2) and 3.2 × 10(1) CFU, respectively, resulted in 100% mortality, demonstrating the virulence of hvKP1 and its ability to cause infection at a low dose. These data strongly support that aerobactin accounts for increased siderophore production in hvKP compared to cKP (a potential defining trait) and is an important virulence factor.

MATERIALS
Product Number
Brand
Product Description
C3518
Sigma-Aldrich
Carbonyl iron, ≥97% Fe basis
413054
Sigma-Aldrich
Iron, granular, 10-40 mesh, >99.99% trace metals basis
356824
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Iron, wire, diam. 1.0 mm, ≥99.9% trace metals basis
338141
Sigma-Aldrich
Iron, foil, thickness 0.25 mm, ≥99.99% trace metals basis
GF21695722
Iron, wire reel, 2m, diameter 0.13mm, hard, 99.99+%
GF64363372
Iron, foil, light tested, 25x25mm, thickness 0.01mm, 99.99+%
12310
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Iron, ≥99%, reduced, powder (fine)
GF61762642
Iron, foil, 4mm disks, thickness 0.01mm, 99.85%
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Iron, foil, 25mm disks, thickness 0.9mm, as rolled, 99.5%
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Iron, foil, 2m coil, thickness 0.25mm, hard, 99.5%
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Iron, foil, 4mm disks, thickness 1.0mm, as rolled, 99.5%
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Iron, foil, 4mm disks, thickness 0.025mm, hard, 99.5%
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Iron, foil, 25mm disks, thickness 0.125mm, as rolled, 99.99+%
GF11791919
Iron, foil, 4mm disks, thickness 0.38mm, hard, 99.5%
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Iron, rod, 500mm, diameter 3.0mm, as drawn, 99.99+%
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Iron, rod, 50mm, diameter 10.0mm, as drawn, 99.99+%
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Iron, foil, 10mm disks, thickness 0.006mm, 99.85%
GF61886571
Iron, tube, 500mm, outside diameter 3.2mm, inside diameter 2.2mm, wall thickness 0.5mm, as drawn, 99.8%
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Iron, foil, 300x300mm, thickness 0.38mm, hard, 99.5%
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Iron, tube, 1000mm, outside diameter 2.0mm, inside diameter 1.08mm, wall thickness 0.46mm, as drawn, 99.5%
GF95708717
Iron, foil, 100x100mm, thickness 0.38mm, hard, 99.5%
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Iron, rod, 500mm, diameter 6.35mm, as drawn, soft ingot 99.8%
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Iron, foil, 100x100mm, thickness 0.5mm, as rolled, 99.99+%
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Iron, tube, 1000mm, outside diameter 1.0mm, inside diameter 0.8mm, wall thickness 0.1mm, as drawn, 99.5%
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Iron, rod, 200mm, diameter 6.35mm, as drawn, 98+%
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Iron, foil, 50x50mm, thickness 0.25mm, hard, 99.5%
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Iron, foil, 50x50mm, thickness 0.5mm, as rolled, 99.99+%
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Iron, tube, 200mm, outside diameter 2.0mm, inside diameter 1.08mm, wall thickness 0.46mm, as drawn, 99.5%
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Iron, tube, 100mm, outside diameter 25.0mm, inside diameter 21mm, wall thickness 2mm, annealed, 99.5%
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