Menkes' disease: case report

Agertt, Fabio; Crippa, Ana C. S.; Lorenzoni, Paulo José; Scola, Rosana Hermínia; Bruck, Isac; Paola, Luciano De; Silvado, Carlos Eduardo; Werneck, Lineü Cesar

doi:10.1590/s0004-282x2007000100032

Cited by 22 publications

(14 citation statements)

References 15 publications

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“…In light of our findings, it is notable that bacterial infections, especially those of the respiratory tract, are commonly reported in infants with Menkes disease, in whom genetic mutations in the ATP7A gene give rise to copper deficiency (43)(44)(45)(46). However, it is uncertain whether this susceptibility to infections arises from defects in ATP7A-dependent activities of macrophages or impairment of other copper-requiring processes.…”

Section: Discussionmentioning

confidence: 70%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

421

521

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Copper is an essential micronutrient that is necessary for healthy immune function. This requirement is underscored by an increased susceptibility to bacterial infection in copper-deficient animals; however, a molecular understanding of its importance in immune defense is unknown. In this study, we investigated the effect of proinflammatory agents on copper homeostasis in RAW264.7 macrophages. Interferon-␥ was found to increase expression of the high affinity copper importer, CTR1, and stimulate copper uptake. This was accompanied by copper-stimulated trafficking of the ATP7A copper exporter from the Golgi to vesicles that partially overlapped with phagosomal compartments. Silencing of ATP7A expression attenuated bacterial killing, suggesting a role for ATP7A-dependent copper transport in the bactericidal activity of macrophages. Significantly, a copper-sensitive mutant of Escherichia coli lacking the CopA copper-transporting ATPase was hypersensitive to killing by RAW264.7 macrophages, and this phenotype was dependent on ATP7A expression. Collectively, these data suggest that copper-transporting ATPases, CopA and ATP7A, in both bacteria and macrophage are unique determinants of bacteria survival and identify an unexpected role for copper at the hostpathogen interface.

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Section: Discussionmentioning

confidence: 70%

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

White

Lee

Kambe

et al. 2009

Journal of Biological Chemistry

421

521

View full text Add to dashboard Cite

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“…Whether CTR1 and ATP7A play critical roles in killing other bacterial pathogens such as M. tuberculosis and S. typhimurium in vitro and in vivo is the subject of ongoing investigations. However, consistent with a role for ATP7A in immune defense, it is notable that patients with Menkes disease who lack a functional ATP7A copper transporter have increased susceptibility to infection of the bladder and lungs (81)(82)(83)(84).…”

Section: Importance Of Mammalian Copper Transporters In Macrophage Bamentioning

confidence: 82%

Copper Homeostasis at the Host-Pathogen Interface

Hodgkinson

Petris

2012

Journal of Biological Chemistry

251

232

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The trace element copper is indispensable for all aerobic life forms. Its ability to cycle between two oxidation states, Cu 1؉ and Cu 2؉ , has been harnessed by a wide array of metalloenzymes that catalyze electron transfer reactions. The metabolic needs for copper are sustained by a complex series of transporters and carrier proteins that regulate its intracellular accumulation and distribution in both pathogenic microbes and their animal hosts. However, copper is also potentially toxic due in part to its ability to generate reactive oxygen species. Recent studies suggest that the macrophage phagosome accumulates copper during bacterial infection, which may constitute an important mechanism of killing. Bacterial countermeasures include the up-regulation of copper export and detoxification genes during infection, which studies suggest are important determinants of virulence. In this minireview, we summarize recent developments that suggest an emerging role for copper as an unexpected component in determining the outcome of host-pathogen interactions.

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“…Human infants with the copper deficiency disorder, Menkes disease, exhibit higher incidences of lung and bladder infection 70-73 . Copper deficiency in animals has been shown to impair the production of antibody-producing cells 74 , suppress the respiratory burst of neutrophils and macrophages 7576 , and limit the ability of the host to combat infection 77-82 .…”

Section: Introductionmentioning

confidence: 99%

Copper tolerance and virulence in bacteria

2015

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Copper (Cu) is an essential trace element for all aerobic organisms. It functions as a cofactor in enzymes that catalyze a wide variety of redox reactions due to its ability to cycle between two oxidation states, Cu(I) and Cu(II). This same redox property of copper has the potential to cause toxicity if copper homeostasis is not maintained. Studies suggest that the toxic properties of copper are harnessed by the innate immune system of the host to kill bacteria. To counter such defenses, bacteria rely on copper tolerance genes for virulence within the host. These discoveries suggest bacterial copper intoxication is a component of host nutritional immunity, thus expanding our knowledge of the roles of copper in biology. This review summarizes our current understanding of copper tolerance in bacteria, and the extent to which these pathways contribute to bacterial virulence within the host.

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Menkes' disease: case report

Cited by 22 publications

References 15 publications

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

A Role for the ATP7A Copper-transporting ATPase in Macrophage Bactericidal Activity

Copper Homeostasis at the Host-Pathogen Interface

Copper tolerance and virulence in bacteria

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