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Category: Fungi and Fungal Pathogenesis
Virulence Factors in Black Molds with Emphasis on Melanin, Chitin, and Wangiella as a Molecularly Tractable Model, Page 1 of 2
< Previous page | Next page > /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap28-1.gif /docserver/preview/fulltext/10.1128/9781555815776/9781555813680_Chap28-2.gifAbstract:
Wangiella dermatitidis is an asexual polymorphic mold that is arguably the most studied black fungal pathogen of humans. This chapter provides a brief overview of these fungi, summarizes certain salient historical facts about W. dermatitidis, including the main attributes that contributed to its rise to model status. It then reviews results of recent molecular genetic studies that are primarily aimed at the cell wall virulence factors melanin and chitin. The advances described are intended to motivate others to determine whether the molecular findings with the model have relevance to the other, less well studied black mold pathogens. Elucidation of the 1,8-dihydroxynaphthalene (1,8-DHN) melanin biosynthetic pathway in W. dermatitidis initially resulted from the use of the specific pathway inhibitor tricyclazole and the identification of key pathway intermediates, secretion products, and enzymes of the wild-type strain and a few mutant strains (Mel) with obvious pigmentation defects. Decreased virulence due to defective 1,8-DHN melanin biosynthesis in W. dermatitidis was initially detected in the hypopigmented Mel strain mel3, which is albino because of an inability to synthesize 1,3,6,8-tetrahydroxynapththalene (1,3,6,8-THN). It is important to note that some albino Mel strains become pink to orange when exposed to light of relatively high intensity for extended periods.
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Representative morphotypes of W. dermatitidis. (A) Logarithmic-phase yeast; (B) pseudohyphal yeast; (C) sclerotic cell that first produced a branching moniliform hypha which in turn produced true hyphae, both of which are producing yeast-like cells (blastospores) at septal regions that are in various stages of disarticulation; (D) cells in panel A at about ×3 higher magnification; (E) isotropically enlarging sclerotic cells and sclerotic bodies in various stages of septation; (F) a multicellular sclerotic body produced in acid-rich medium undergoing fission. The bar in panel A represents about 5μm and also applies to panels B and C, whereas the bar in panel D represents about 15μm and also applies to panels E and F.
Schematic representation of the morphotypes of W. dermatitidis induced in vitro by various factors. Starting with a polarized budding yeast cell or conidium, some conditions induce pseudohypha development because of the lack of yeast cell separation while others induce the loss of polarity that leads to transient or prolonged isotropic development. The latter produces the morphotypes known as sclerotic cells, planate cells, and sclerotic bodies. Return of the isotropic forms to conditions conducive to normal yeast growth usually leads to polarity reestablishments that result in moniliform and true hyphal outgrowths. Blastoconidia are then produced directly from hyphae and phialoconidia and annelloconidia are produced from conidiophores, both of which can reestablish budding yeast populations. The morphotypes are not drawn to scale (note the differences in scale bars): the sclerotic cells and sclerotic bodies are often three to many times larger than mother yeast cells or conidia and usually have thicker walls enriched with both melanin and chitin. The ∼ in the cell walls indicates chitin. Adapted from reference 120 , Fig. 1 .
Selected etiological agents of mycoses caused by black molds a
Summary of chitin synthase gene disruptions in wild-type Wangiella a