Pathogenic roles for fungal melanins

Authors
Citation
Es. Jacobson, Pathogenic roles for fungal melanins, CLIN MICROB, 13(4), 2000, pp. 708
Citations number
105
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Microbiology
Journal title
CLINICAL MICROBIOLOGY REVIEWS
ISSN journal
0893-8512 → ACNP
Volume
13
Issue
4
Year of publication
2000
Database
ISI
SICI code
0893-8512(200010)13:4<708:PRFFM>2.0.ZU;2-M
Abstract
Melanins represent virulence factors for several pathogenic fungi; the numb er of examples is growing. Thus, albino mutants of several genera (in one c ase, mutated precisely in the melanizing enzyme) exhibit decreased virulenc e in mice. We consider the phenomenon in relation to known chemical propert ies of melanin, beginning with biosynthesis from orthohydroquinone precurso rs which, I-when oxidized enzymatically to quinones, polymerize spontaneous ly to melanin. It follows that melanizing intermediates are cross-linking r eagents; melanization stabilizes the external cell wall against hydrolysis and is thought to determine semipermeability in the osmotic ram (the appres sorium) of certain plant pathogens. Polymeric melanins undergo reversible o xidation-reduction reactions between cell wall-penetrating quinone and hydr oquinone oxidation states and thus represent polymeric redox buffers; using strong oxidants, it is possible to titrate the melanin on living cells and thereby demonstrate protection conferred by melanin in several species. Th e amount of buffering per cell approximately neutralizes the amount of oxid ant generated by a single macrophage. Moreover, the intermediate oxidation state, the semiquinone, is a very stable free radical and is thought to tra p unpaired electrons. We have suggested that the oxidation state of externa l melanin may be regulated by external Fe(II). An independent hypothesis ho lds that in Cryptococcus neoformans, an important function of the melanizin g enzyme (apart from melanization) is the oxidation of Fe(II) to Fe(III), t hereby forestalling generation of the harmful hydroxyl radical from H2O2. T hus, problems in fungal pathogenesis have led to evolving hypotheses regard ing melanin functioning.