Melanin is crucial for growth of the black yeast Hortaea werneckii in its natural hypersaline environment

Melanin has an important role in the ability of fungi to survive extreme conditions, like the high NaCl concentrations that are typical of hypersaline environments. The black fungus Hortaea werneckii that has been isolated from such environments has 1,8-dihydroxynaphthalene-melanin incorporated into the cell wall, which minimises the loss of glycerol at low NaCl concentrations. To further explore the role of melanin in the extremely halotolerant character of H. werneckii, we studied the effects of several melanin biosynthesis inhibitors on its growth, pigmentation and cell morphology. The most potent inhibitors were a 2,3-dihydrobenzofuran derivative and tricyclazole, which restricted the growth of H. werneckii on high-salinity media, as shown by growth curves and plate-drop assays. These inhibitors promoted release of the pigments from the H. werneckii cell surface and changed the medium colour. Inhibitor-treated H. werneckii cells exposed to high salinity showed both decreased and increased cell lengths. We speculate that this absence of melanin perturbs the integrity of the cell wall in H. werneckii, which affects its cell division and exposes it to the harmful effects of high NaCl concentrations. Surprisingly, melanin had no effect on H. werneckii survival under H₂O₂ oxidative stress.     

Comparative Analysis of Melanins and Melanosomes Produced by Various Coat Color Mutants

Pigmentation in the skin, hair, and eyes of animals is influenced by a number of genes that modulate the activity of melanocytes, the intervention of enzymatic controls at different stages of the melanogenic process, and the physico-chemical properties of the final pigment. The results of combined phenotypic, ultrastructural, biochemical, and chemical analyses of hairs of a variety of defined genotypes on a common genetic background performed in this study are consistent with the view that pigmentation of dark to black hairs results from the incorporation of eumelanin pigments whereas that of yellow hairs results from the incorporation of eu- and pheomelanins. It is also clear that relatively minor differences in melanin content can have dramatic effects on visible hair color. A good correlation was found for expression of (and enzyme activities associated with) TRP1 and TRP2 with eumelanin synthesis and eumelanosome production.     

Melanin and novel melanin precursors from Aeromonas media

Many bacteria produce reddish brown to black pigments and some of these have been characterised. This report describes the isolation and characterisation of a diffusible brown melanin-like pigment from the bacterium Aeromonas media. Physico-chemical testing suggested that the pigment is a true melanin. New butanol-soluble yellow, red and brown pigments were isolated from the A. media strain under reducing conditions during melanogenesis and these pigments were shown to be unstable precursors of the polymeric brown melanin product.     

bFGF与黑色素关系的研究进展

碱性成纤维细胞生长因子(bFGF)是一种具有多种生物学效应的细胞因子。目前对bFGF与黑色素关系的研究主要集中在bFGF对黑色素细胞的生长产生的影响和对黑色素生成的调控等方面,并进而探讨研究治疗黑色素相关疾病的机理,综述了在这些方面的研究进展。     

The threat of emerging and re-emerging pathogenic Sporothrix species

Mycopathologia - Sporotrichosis is a neglected subcutaneous mycosis of humans and animals acquired by traumatic inoculation of soil and plant material (classical route) contaminated with infectious...     

Interference of melanin in the susceptibility profile of Sporothrix species to amphotericin B

BackgroundThe presence of melanin in the fungal cell is a major virulence factor of the genus Sporothrix since it protects the fungal cells against the defense systems.AimsThe present study aimed to investigate the interference of melanin in the susceptibility of Sporothrix brasiliensis and Sporothrix schenckii sensu stricto to amphotericin B and itraconazole, drugs recommended as therapy for disseminated and subcutaneous sporotrichosis, respectively.MethodsYeast cells were cultivated in minimal medium with or without l-DOPA in order to induce the production of melanin. Microdilution and killing assay methods were used to determine the antifungal activity against yeast cells with different amounts of melanin.ResultsThe killing assay showed that melanization protected isolates within the S. schenckii complex from amphotericin B, particularly in the lower concentrations tested.ConclusionsStudies combining amphotericin B and inhibitors of melanin are required in order to avoid this effect.     

On the Melanization of the Rat's Eye

Electron-microscopic study of the size of the melanosomes, the mean percentage of melanosomal profile area (MPMA) of the cells, and the duration of melanogenesis in the pigmented layers of the rat's eye (inbred strain BDE/Han) revealed the following: 1) The melanosomes in the cells of the retina vary in size and shape in different locations of the eye. The MPMA of the cells also differs. Only in the two layers of the iris epithelium do the minor diameters of the melanosomes not differ significantly from each other, but the MPMA of the cells is different. The pigmented outer layer of the ciliary epithelium stands out on account of its especially large, round melanosomes. 2) The melanosomes of the uveal melanocytes are uniformly small but exhibit the largest MPMA. 3) Only in the pigment epithelium of the fundus does melanogenesis cease in the fifth week of life. As a result the MPMA decreases. In the other areas of the pigmented epithelium and the uvea tyrosinase activity and premelanosomes are present from the new-born to the adult animal. These signs indicate continued melanogenesis. 4) Compound melanosomes are present in all pigmented locations of the eye. Giant melanosomes occur regularly only in the outer layer of the retina.     

Melanin and HIV in sub-Saharan Africa

HIV is common in sub-Saharan Africa. Sexually transmitted bacterial and fungal infections increase the chance of HIV infection. Melanin can prevent the penetration of skin and mucus membranes by microorganisms, and soluble melanin can inhibit HIV replication. We suggest that melanin may reduce the incidence of HIV infection through venereally acquired skin lesions, thus reducing the risk of sero-conversion and slow the progress to AIDS. Indigenous sub-Saharan peoples are highly melanized, but there is pigment variation between populations. We show that skin reflectance, a negative correlate of melanin, is positively associated with adult rate of HIV in sub-Saharan countries. There is no such relationship in populations outside sub-Saharan Africa. We suggest that melanin concentration in black people may correlate with resistance to HIV infection.     

Characterization of the Neurospora crassa DHN melanin biosynthetic pathway in developing ascospores and peridium cells

Neurospora crassa contains all four enzymes for the synthesis of DHN (dihydroxynaphthalene), the substrate for melanin formation. We show that the DHN melanin pathway functions during N. crassa female development to generate melanized peridium and ascospore cell walls. N. crassa contains one polyketide synthase (PER-1), two polyketide hydrolases (PKH-1 and PKH-2), two THN (tetrahydroxynaphthalene) reductases (PKR-1 and PKR-2), and one scytalone dehydratase (SCY-1). We show that the PER-1, PKH-1, PKR-1 and SCY-1 are required for ascospoer melanization. We also identified the laccase that functions in the conversion of DHN into melanin via a free radical oxidative polymerization reaction, and have named the gene lacm-1 (laccase for melanin formation-1). In maturing perithecia, we show that LACM-1 is localized to the peridium cell wall space while the DHN pathway enzymes are localized to intracellular vesicles. We present a model for melanin formation in which melanin is formed within the cell wall space and the cell wall structure is similar to “reinforced concrete” with the cell wall glucan, chitin, and glycoproteins encased within the melanin polymer. This arrangement provides for a very strong and resilient cell wall and protects the glucan/chitin/glycoprotein matrix from digestion from enzymes and damage from free radicals.     

Interaction Between Chemicals and Melanin

Various drugs and other chemicals, such as organic amines, metals, polycyclic aromatic hydrocarbons, etc., are bound to melanin and retained in pigmented tissues for long periods. The physiological significance of the binding is not evident, but it has been suggested that the melanin protects the pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which then are slowly released in nontoxic concentrations. Long-term exposure, on the other hand, may build up high levels of noxious chemicals, stored on the melanin, which ultimately may cause degeneration in the melanin-containing cells, and secondary lesions in surrounding tissues. In the eye, e.g., and in the inner ear, the pigmented cells are located close to the receptor cells, and melanin binding may be an important factor in the development of some ocular and inner ear lesions. In the brain, neuromelanin is present in nerve cells in the extrapyramidal system, and the melanin affinity of certain neurotoxic agents may be involved in the development of parkinsonism, and possibly tardive dyskinesia. In recent years, various carcinogenic compounds have been found to accumulate selectively in the pigment cells of experimental animals, and there are many indications of a connection between the melanin affinity of these agents and the induction of malignant melanoma.     

Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview

Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles (“ghosts”) can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic dimorphic fungi including Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides posadasii. Melanization appears to contribute to virulence by reducing the susceptibility of melanized fungi to host defense mechanisms and antifungal drugs.     

Melanin biosynthesis and the metabolism of flaviolin and 2-hydroxyjuglone inWangiella dermatitidis

Melanin biosynthesis in the human pathogenWangiella dermatitidis was inhibited by tricyclazole, causing pentaketide melanin metabolites to accumulate in the cultures. One of these metabolites, scytalone, was racemic and thus different than the (+)-enantiomer fromVerticillium dahliae. An albino mutant ofW. dermatitidis metabolized scytalone to a pigment ultrastructurally identical to wild-type melanin. Cell-free homogenates of the wild type carried out typical reductive and dehydrative reactions with known melanin intermediates and the reductive reactions were inhibited by tricyclazole. Other reductive and dehydrative reactions that utilize flaviolin and 2-hydroxyjuglone were studied anaerobically with homogenates from both the wild type and the albino mutant. The homogenates converted flaviolin to 5-hydroxyscytalone and products identical to those obtained from 2-hydroxyjuglone. The albino, in culture, carried out the same reactions with 2-hydroxyjuglone but metabolized flaviolin to a number of unknown colored products apparently through oxidative reactions. Similarities between the melanin pathway and the flaviolin and 2-hydroxyjuglone branch pathways are discussed and tricyclazole is shown to inhibit reductive reactions with naphthols in the three pathways.Abbreviations DHN dihydroxynaphtalene - HJ hydroxyjuglone - THT trihydroxytetralone - THN trihydroxynaphthalene or tetrahydroxynaphthalene - DTT dithiothreitol - HS hydroxyscytalone - PHN pentahydroxynaphthalene     

Melanin Standard Method: Titrimetric Analysis

Melanin isolated from the ink sac of Sepia officinalis (Sepia melanin) has been proposed as a standard for natural eumelanin, and a standard mild isolation and purification protocol for Sepia melanin has been developed (Zeise, doctoral dissertation, Johns Hopkins University, 1991). The goal of the present work, developed using Sepia melanin, was to quantify the bioavailable carboxylic acid groups present in melanin particles. Bioavailability is governed by the accessibility of carboxy groups to the surrounding biological milieu, and is expressed as microequivalents of carboxy group per gram of melanin. The present work was carried out using an heterogeneous slurry of melanin in a nonaqueous system. A standard acidic titrant, and an automatic titrator operating in an equilibrium titration mode were used to characterize and quantify the carboxy group content of Sepia melanins and several other commonly used melanins purified by a standard method (Zeise et al., Pigment Cell Res. [Suppl] 2:48–53, 1992).     

Recent progress in cellulose biosynthesis

Cellulose comprises the major polymer of the plant cell wall. It consists of a set of parallel chains composed of glucans and these chains are highly oriented to form a structure known as a microfibril. The orientation of the microfibrils controls the extension of the direction of the plant cell. Extensive studies on the cellulose biosynthesis have been carried out for over three decades, and recently (1996) genes for cellulose biosynthesis in plants (CesA) were isolated. In the year 2002, a specific primer for cellulose biosynthesis reaction has been discovered and cellulose synthetic activity has been also confirmed by recombinant protein derived from the plant CesA gene. Furthermore, other proteins involved in cellulose biosynthesis besides CesA proteins were also proposed at the same time. One of these proteins, Korrigan cellulase, was suggested to act by removing sitosterol from the primer for biosynthesis reaction of cellulose. A membrane-bound sucrose synthase was also suggested to provide UDP-glucose as a substrate for cellulose biosynthesis. On the basis of these results, a new pathway for cellulose biosynthesis was proposed. Now, the research field of cellulose biosynthesis is facing a major turning point. Electronic Publication     

神经皮肤黑变病中黑色素的来源初探

目的探讨食蟹猴神经皮肤黑变病（NCM）中黑色素的来源。方法收集北京协和医学院比较医学中心病理室食蟹猴神经皮肤黑变病的病理学标本一例,复习其病理切片并辅助免疫组化及电镜技术对黑色素的来源做进一步探讨。结果皮肤病理检查显示真皮内黑色素主要由黑色素细胞产生,黑色素细胞CD31免疫组化染色阴性。脑膜的组织病理学显示脑膜下黑色素主要由黑色素细胞产生,黑色素细胞CD31免疫组化染色阴性。脑实质的组织病理学显示其黑色素由黑色素细胞和血管内皮细胞产生,CD31免疫组化染色显示含有黑色素的血管内皮细胞呈阳性着色。电镜检查结果同样显示血管内皮细胞内可见黑色素小体沉积。结论我们在世界上首次揭示了食蟹猴NCM大脑中血管内皮细胞可产生黑色素,这给内皮细胞增加了一项新的功能。     

The Effect of Sodium Iodate and Melanin on the Formation of Glyoxylate

Sodium iodate damages retinal pigment epithelium specifically, but the reason for this specificity is not well understood. The work reported here describes an effect of sodium iodate on melanin, a major component of the retinal pigment epithelium. Sodium iodate increases the ability of melanin to convert glycine to glyoxylate. Almost ten times as much glyoxylate is formed when sodium iodate is present compared to the amount formed with melanin alone, although iodate alone does not convert glycine to glyoxylate. A chemical reaction between sodium iodate and melanin is suggested as a partial explanation of the specificity of iodate toxicity towards retinal pigment epithelium.     

野生Bc菌株产黑色素的研究

Bc58是一株野生蜡状芽抱杆菌菌株,经L-酪氨酸诱导后可产生红棕色色素。通过红外光谱及各种化学测定证明该色素与Sigma公司标准黑色素（Melanin）的性质相似。生测结果显示添加Bc58黑色素的Bt制剂经紫外照射5h后的LC50为16．1μg／mL,与未经紫外照射的Bt制剂的LC50 15．2μg／mL基本相同,而比未添加黑色素的Bt制剂经紫外照射后的杀虫毒力高出近1倍。经SDS—PAGE检测表明该黑色素可保护苏云金杆菌晶体蛋白在紫外光下基本不降解,表明Bc58黑色素是一种优良的紫外保护剂。     

From Gene to Protein: Determination of Melanin Synthesis

Melanin production in mammals is regulated at a variety of levels (tissue, cellular, and subcellular), and many gene loci are involved in the determination of color patterns directed by the melanocyte. Many of the genes involved in these complex processes have now been cloned, and even the simplest mutation can lead to dramatic changes in the phenotype of the individual. Many, if not all, of the pigment related genes have pleiotropic effects on the development and differentiation of the organism, and perhaps because of this, the melanocyte is evolving as an important model for the study of gene regulation and action at the functional level. In view of the importance of pigmentation as a photoprotective barrier and as a cosmetic factor affecting appearance and social acceptance, the importance of these studies seems destined to increase significantly in the future.