The effect of melanin on iron associated decomposition of hydrogen peroxide

Pilas, Barbara; Sarna, Tadeusz; Kalyanaraman, B.; Swartz, Harold M.

doi:10.1016/0891-5849(88)90049-4

Cited by 131 publications

(97 citation statements)

References 18 publications

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“…Transition metals are known to associate with melanin (20); indeed, in the presence of strong chelators of Fe(II) and Fe(III) and in the absence of initial Fe(II), melanin generates Fe(II) from Fe(III) (17), a reaction which we also have observed (16). However, the reverse reaction, reduction of melanin by Fe(II), has not previously been shown, and until very recently it has not been possible directly to monitor the oxidation state of melanin itself as it reacts with redox reagents.…”

Section: Discussionsupporting

confidence: 59%

“…The observed reduction of Fe(III) to Fe(II) on the external surface of C. neoformans appears to provide one such electron transport mechanism. One might ask whether reduction of Fe(III) might have a deleterious effect upon the pathogen, based upon the propensity of Fe(II) to react with H 2 O 2 and generate potentially harmful hydroxyl radicals; however, binding of Fe(II) by melanin suppresses this reaction (17), while the hydroxyl radical appears to be harmlessly absorbed by melanin (22). Inasmuch as secreted low-molecular-weight reductants can themselves neutralize extracellular oxidants without mediation by melanin, an important use of melanin may be its ability to concentrate and immobilize a quantity of reducing equivalents just outside the surface of the cell.…”

Section: Discussionmentioning

confidence: 99%

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Redox buffering by melanin and Fe(II) in Cryptococcus neoformans

Jacobson

Hong

1997

J Bacteriol

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Melanin is a fungal extracellular redox buffer which, in principle, can neutralize antimicrobial oxidants generated by immunologic effector cells, but its source of reducing equivalents is not known. We wondered whether Fe(II) generated by the external ferric reductase of fungi might have the physiologic function of reducing fungal melanin and thereby promoting pathogenesis. We observed that exposure of a melanin film electrode to reductants decreased the open-circuit potential (OCP) and reduced the area of a cyclic voltammetric reduction wave whereas exposure to oxidants produced the opposite effects. Exposure to 10, 100, 1,000 or 10,000 M Fe(II) decreased the OCP of melanin by 0.015, 0.038, 0.100, and 0.120 V, respectively, relative to a silver-silver chloride standard, and decreased the area of the cyclic voltammetric reduction wave by 27, 35, 50, and 83%, respectively. Moreover, exposure to Fe(II) increased the buffering capacity by 44%, while exposure to millimolar dithionite did not increase the buffering capacity. The ratio of the amount of bound iron to the amount of the incremental increase in the following oxidation wave was approximately 1.0, suggesting that bound iron participates in buffering. Light absorption by melanin suspensions was decreased 14% by treatment with Fe(II), consistent with reduction of melanin. Light absorption by suspensions of melanized Cryptococcus neoformans was decreased 1.3% by treatment with Fe(II) (P < 0.05). Cultures of C. neoformans generated between 2 and 160 M Fe(II) in culture supernatant, depending upon the strain and the conditions [the higher values were achieved by a constitutive ferric reductase mutant in high concentrations of Fe(III)]. We infer that Fe(II) can reduce melanin under physiologic conditions; moreover, it binds to melanin and cooperatively increases redox buffering. The data support a model for physiologic redox cycling of fungal melanin, whereby electrons exported by the yeast to form extracellular Fe(II) maintain the reducing capacity of the extracellular redox buffer.Leukocytes attack pathogens with a flux of secreted strong oxidants (1). Thus, any extracellular microbial product which neutralizes oxidants is likely to protect the pathogen and promote invasive disease. Melanin, an extracellular redox buffer composed of polymerized catechols (5,14,15,21), is a virulence factor for certain pathogenic fungi (3, 11). Its ability to neutralize strong oxidants is supported by several types of evidence: mutants of Cryptococcus neoformans selected for sensitivity to oxidants exhibit albinism (8); nonmelanized wildtype cells or mutants selected for albinism exhibit sensitivity to oxidants (9, 18); and melanin neutralizes oxidants and protects the melanized fungi C. neoformans, Wangiella dermatididis, and Alternaria alternata from killing by hypochlorite and by permanganate (8, 9). Thus, melanin may function as chemical armor in invasive disease. We reasoned that maintenance of the reducing capacity of extracellular melanin may be an important aggressive f...

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Redox buffering by melanin and Fe(II) in Cryptococcus neoformans

Jacobson

Hong

1997

J Bacteriol

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“…In the presence of the strong chelator, EDTA, melanin does not bind Fe(II) and does not inhibit hydroxyl radical formation. If Fe(III) is chelated by EDTA, melanin reduces but does not bind Fe(III); the resulting Fe(II) reacts with H 2 O 2 to produce hydroxyl radicals (57). Thus, in the presence of the stronger chelator, EDTA, melanin does not bind Fe(III) effectively but does serve as a reducing agent for Fe(III).…”

Section: Interaction Of Melanin With Metals Chelation Versus Oxidatiomentioning

confidence: 99%

Pathogenic Roles for Fungal Melanins

Jacobson

2000

Clinical Microbiology Reviews

376

277

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“…Such a function is effectively served by melanin, which acts as a cation exchange polymer to protect tissues against oxidizing and reducing conditions and trap free-radicals (Sealy et al, 1980;Crippa et al, 1989). Thus, the binding of eumelanin to metal ions modifies their redox potentials and alters significantly their biological interaction with HzOz, thereby limiting the production of 'OH (Korytowski et al, 1986;Korytowski and Sarna, 1990;Pilas et al, 1988;Hubbard-Smith et al, 1992;Swartz et al, 1992). Thus, functions performed by melanins in insect immunity include not only the generation and site specific localization (i.e., the parasite surface) of cytotoxic molecules, but also the detoxification of these substances, preventing their dissemination throughout the open circulatory system of the insect host.…”

Section: Melanization and Site-directed Cytotoxicity Against Parasitesmentioning

confidence: 99%