Melanized and non‐melanized multicellular form mutants of <i>Wangiella dermatitidis</i> in mice: mortality and histopathology studies

Dixon, Dennis R.; Migliozzi, Joseph A.; Cooper, Chester R.; Solis, Otelo G.; Breslin, B; Szaniszlo, Paul J.

doi:10.1111/j.1439-0507.1992.tb00814.x

Cited by 51 publications

(9 citation statements)

References 15 publications

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“…Elimination of melanin production by the infrequently encountered dematiaceous fungus Wangiella dermatitidis is associated with diminished ability to produce invasive hyphal forms, increased susceptibility to neutrophil killing, and virulence in mouse models of infection 29, 30. Non-melanized conidial mutants of the thermally-dimorphic fungal pathogen Sporothrix schenckii show increased susceptibility to killing by ROS, reactive nitrogen species or UV light 31.…”

Section: Melanin In Cryptococcus Neoformans and Aspergillus Fumigatusmentioning

confidence: 99%

Color me bad: microbial pigments as virulence factors

Liu

Nizet

2009

Trends in Microbiology

304

227

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A hallmark feature of several pathogenic microbes is the distinctive color of their colonies when propagated in the clinical laboratory. Such pigmentation comes in a variety of hues, and has often proven useful in presumptive clinical diagnosis. Recent advances in microbial pigment biochemistry and the genetic basis of pigment production has sometimes revealed a more sinister aspect to these curious materials that change the color of reflected light by selective light absorbance. In many cases, the microbial pigment contributes to disease pathogenesis by interfering with host immune clearance mechanisms or by exhibiting pro-inflammatory or cytotoxic properties. Here, we review several examples of pigments that promote microbial virulence, including the golden staphyloxanthin of Staphylococcus aureus, the blue-green pyocyanin of Pseudomonas spp., and the dark brown or black melanin pigments of Cryptococcus neoformans and Aspergillus spp. Targeted pigment neutralization may represent a viable concept to enhance treatment of certain difficult infectious disease conditions. Microbes of colorColors are vital to the sensing of the environment and have evolved in higher living organisms to guide their interactions with others. For example, it is well appreciated that many birds exhibit brightly colored plumage to attract members of the opposite sex, that a chameleon's adaptation to surrounding color is an important means of camouflage, and that the bright coloration of the poison dart frog warn potential predators to stay away. But such explanations cannot be offered to explain why certain microorganisms are pigmented. Since they lack color perception, one must assume evolutionary selective pressures behind the acquisition of pigments that promotes survival independent of their light absorbance, reflection or emission spectral properties (Box 1).Because colors often provide an easy way of identifying certain microbes, they are often coined in names of species. For example, Rosenbach in 1884 named the golden-colored pathogen Staphylococcus aureus (aureus = "golden", Latin) to distinguish it from nonpigmented staphylococci of the resident skin microflora that he named Staphylococcus alba (alba = "white", Latin) 1 . Likewise, the blue-green Pseudomonas species not infrequently found in the lungs of cystic fibrosis patients is given the name aeruginosa, which derives from a Latin word Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. With biotechnological advances, contemporary researchers are in position to study the molecular genetic and biochemical basis for microbial color...

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Section: Melanin In Cryptococcus Neoformans and Aspergillus Fumigatusmentioning

confidence: 99%

Color me bad: microbial pigments as virulence factors

Liu

Nizet

2009

Trends in Microbiology

304

227

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“…Considerable work has been done to elucidate the virulence potentials of several fungi (dematiaceous and nondematiaceous) that contain melanin, notably Aspergillus fumigatus, Cryptococcus neoformans, E. dermatiditis, and S. prolificans (123,134,201,203,205,284,428,549,573,653,671,730,756). There are multiple proposed mechanisms by which melanin may act as a virulence factor (109,324,375).…”

Section: Role Of Melaninmentioning

confidence: 99%

“…These multiple functions may help explain the pathogenic potential of some dematiaceous fungi, even in immunocompetent hosts. Specifically, in E. dermatitidis, disruption of melanin production leads to markedly reduced virulence in animal models and restriction of hyphal growth (103,201,203,428). However, hyphae of S. prolificans were found to be more susceptible to damage from neutrophils than A. fumigatus (284).…”

Section: Role Of Melaninmentioning

confidence: 99%

Melanized Fungi in Human Disease

2010

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SUMMARY Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.

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“…Subsequently, the D2HN melanin was found to be polymerized exclusively in the cell walls of W. dermatitidis, and the earliest enzymatic step identified in its synthesis was determined to involve a PKS encoded by the gene WdPKS1 (14,44). Importantly, the pathway has been documented to be a virulence factor in W. dermatitidis by virtue of the finding that all Mel Ϫ mutants tested thus far are less virulent than the wild type in mouse models of acute infection (12,13,14), less resistant to the phagolysosomal activities of human neutrophils (14,33), and more susceptible to antifungal compounds (30). The results of these studies of W. dermatitidis suggest that the D2HN melanins, and possibly also melanins synthesized from L-3,4-dihydroxyphenyalanine, of the more than 100 other dematiaceous pathogens of humans known or suspected to be melanized by D2HN melanin are important to virulence (30,34,35).…”

mentioning

confidence: 99%

New Biosynthetic Step in the Melanin Pathway ofWangiella(Exophiala)dermatitidis: Evidence for 2-Acetyl-1,3,6,8-Tetrahydroxynaphthalene as a Novel Precursor

et al. 2008

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The predominant cell wall melanin of Wangiella dermatitidis, a black fungal pathogen of humans, is synthesized from 1,8-dihydroxynaphthalene (D2HN). An early precursor, 1,3,6,8-tetrahydroxynaphthalene (T4HN), in the pathway leading to D2HN is reportedly produced directly as a pentaketide by an iterative type I polyketide synthase (PKS). In contrast, the bluish-green pigment in Aspergillus fumigatus is produced after the enzyme Ayg1p converts the PKS product, the heptaketide YWA1, to T4HN. Previously, we created a new melanin-deficient mutant of W. dermatitidis, WdBrm1, by random molecular insertion. From this strain, the altered gene WdYG1 was cloned by a marker rescue strategy and found to encode WdYg1p, an ortholog of Ayg1p. In the present study, two gene replacement mutants devoid of the complete WdYG1 gene were derived to eliminate the possibility that the phenotype of WdBrm1 was due to other mutations. Characterization of the new mutants showed that they were phenotypically identical to WdBrm1. Chemical analyses of mutant cultures demonstrated that melanin biosynthesis was blocked, resulting in the accumulation of 2-acetyl-1,3,6,8-tetrahydroxynaphthalene (AT4HN) and its oxidative product 3-acetylflaviolin in the culture media. When given to an albino W. dermatitidis strain with an inactivated WdPKS1 gene, AT4HN was mostly oxidized to 3-acetylflaviolin and deacetylated to flaviolin. Under reduced oxygen conditions, cell-free homogenates of the albino converted AT4HN to D2HN. This is the first report of evidence that the hexaketide AT4HN is a melanin precursor for T4HN in W. dermatitidis.Melanins are dark pigments widely produced by fungi and other organisms. In fungi, they are frequently found in the cell wall. While not essential for growth and development, these complex polymers seem to enhance the survival and competitive abilities of fungi in certain environments. They are composed of various types of phenolic monomers and are often complexed with protein and, less often, carbohydrates (12,22,29). The melanins in fungi are named according to their composition and the way they are synthesized and include dihydroxyphenylalanine melanin, catechol melanin, ␥-glutaminyl-4-hydroxybenzene melanin, and 1,8-dihydroxynaphthalene (D2HN) melanin (23, 26). The best characterized of these fungal melanins is probably D2HN melanin, which is synthesized by related polyketide pathways ( Fig. 1 and 2A and B). The D2HN melanin pathways start with one acetyl-coenzyme A (acetyl-CoA) molecule and four malonyl-CoA molecules, or solely with malonyl-CoA molecules, which undergo a head-totail joining and cyclization catalyzed by an iterative type I polyketide synthase (PKS) to initially form 1,3,6,8-tetrahydroxynaphthalene (T4HN) (16). From T4HN, multiple sequential enzyme-catalyzed steps produce D2HN, which is then polymerized to form melanin by a poorly characterized oxidase/laccase reaction (5,7,22).In Colletotrichum lagenarium, T4HN is made directly from malonyl-CoA by PKS1p, as shown in Fig. 2B (16). In contrast, in the bluis...

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Melanized and non‐melanized multicellular form mutants of Wangiella dermatitidis in mice: mortality and histopathology studies

Cited by 51 publications

References 15 publications

Color me bad: microbial pigments as virulence factors

Color me bad: microbial pigments as virulence factors

Melanized Fungi in Human Disease

New Biosynthetic Step in the Melanin Pathway ofWangiella(Exophiala)dermatitidis: Evidence for 2-Acetyl-1,3,6,8-Tetrahydroxynaphthalene as a Novel Precursor

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