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مواضيع متنوعة أخرى

الانزيمات
General Properties, Virulence, and Classification of Pathogenic Fungi
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p674-678
2026-02-01
20
Fungi have two basic growth forms, as molds and yeasts. Growth in the mold (or mould) form occurs by the production of multicellular branching cylindrical tubules called hyphae that vary in diameter from 2 to 10 µm. Hyphae are extended by apical elongation due to the production of new cell wall growth at the hyphal tips. The mass of intertwined hyphae that accumulates during active growth is a mycelium. Some hyphae are divided into cells by cross-walls or septa, which typically form at regular intervals during hyphal growth. However, members of the Order Mucorales produce hyphae that are rarely septated. Vegetative or substrate hyphae penetrate the supporting medium, anchor the colony, and absorb nutrients. In contrast, aerial hyphae project above the surface of the mycelium and usually bear the reproductive structures of the mold. When a mold is isolated from a clinical specimen, its growth rate, macroscopic appearance, and microscopic morphology are usually sufficient to determine its genus and species. The most helpful phenotypic features are the ontogeny and morphology of the asexual reproductive spores, or conidia (Figures 1–7).
Fig1. Rhizopus. The sporangium of this mold has released its sporangiospores but remains attached to the supporting sporangiophore, and rhizoids are apparent at the base of the sporangiophore. 200×.
Fig2. Cunninghamella bertholletiae. The sporangiospores are produced within sporangiola that are attached to a vesicle and supported by a sporangiophore. 400×.
Fig3. Penicillium. Chains of conidia are generated by phialides, which are supported by a branched conidiophore. The basal conidium is newest. 400×.
Fig4. Scopulariopsis. This chain of conidia was produced by an annellide, which is another type of conidiogenous cell. 400×.
Fig5. A. fumigatus. Phialides form on top of a swollen vesicle at the end of a long conidiophore. The basal conidia are the youngest. Mature conidia have rough walls. 400×.
Fig6. Bipolaris. Dematiaceous mold that produces characteristic thick-walled macroconidia. 400×.
Fig7. Curvularia. Dematiaceous mold that produces characteristic curved macroconidia with distinctly larger central cells. 400×.
Yeasts are single cells, usually spherical to ellipsoid in shape and varying in diameter from 3 to 15 µm. Most yeasts reproduce by budding, which is initiated by a lateral or terminal protrusion of new cell wall growth that enlarges during mitosis. One or more replicated nuclei enter the nascent bud, which subsequently forms a septum and separates from the parent cell. Some species produce buds that characteristically fail to detach and become elongated; this continuation of the budding process produces chains of elongated yeast cells called pseudohyphae. Yeast colonies are usually soft, opaque, 1–3 mm in size, and cream colored. The colonies and microscopic morphology of many species of yeasts appear quite similar, but they can be identified by physiologic tests and a few key morphologic differences. Some species, including several pathogens, are dimorphic and capable of growth as a yeast or mold depending on environmental conditions, such as temperature or available nutrients.
The life cycles of fungi are remarkably versatile. Depending on the fungus, the predominant nuclear chromosomal count may be haploid or diploid. Some species exist entirely by clonal growth or asexual reproduction, and barring spontaneous mutations, every cell will be a genetic clone. Many other species are capable of sexual reproduction, which may or may not require genetically different partners for mating and meiosis. Asexual as well as sexual reproduction can result in the pro duction of spores, which enhance fungal survival. Spores are usually dormant, readily dispersed, more resistant to adverse conditions, and germinate to form vegetative cells when conditions for growth are favorable. Spores derived from asexual or sexual reproduction are termed anamorphic or teleomorphic, respectively. Like vegetative cells, asexual spores are mitotic progeny (ie, mitospores). The medical fungi produce two major types of asexual spores, conidia, which are produced by most pathogenic fungi, and, in the Order Mucorales, sporangiospores (see below and Glossary). Informative features of spores include their ontogeny (some molds produce complex conidiogenic structures) as well as their morphology (size, shape, texture, color, and unicellularity or multicellularity). In some fungi, vegetative cells may transform into conidia (eg, arthro conidia and chlamydospores). In others, conidia are produced by a conidiogenous cell, such as a phialide, which itself may be attached to a specialized hypha called a conidiophore. Sporangiospores result from mitotic replication and spore production within a sac-like structure called a sporangium, which is supported by a sporangiophore.
Certain fungal properties are essential but not necessarily sufficient for pathogenicity, such as the ability to proliferate in the mammalian host. Many virulence factors have evolved to enable pathogenic fungi to withstand or circumvent the defenses and stressful environment of the host. Some of these virulence determinants include morphological transformations, genetic “switching” of metabolic processes in response to the host environment, the production of surface adhesins that bind to host cell membranes, the secretion of enzymes that attack host substrates (eg, catalase, aspartyl proteinases, and phospholipases), cell wall components that resist phagocytosis (eg, α-(1,3)-glucan, melanin, the capsule of Cryptococcus), and the formation of biofilms. Specific examples are provided in this chapter’s descriptions of several mycoses.
Fungi have an essential rigid cell wall that determines their shape and protects them from osmotic and other environmental stresses. Cell walls are composed largely of carbohydrate layers— long chains of polysaccharides—as well as glycoproteins and lip ids. Some sugar polymers are found in the cell walls of many fungi, such as chitin (an unbranched polymer of β-1,4-linked N-acetylglucosamine); glucans, which are glucose polymers (eg, α-1,3-glucan, β-1,3-glucan, and β-1,6-glucan); and mannans, polymers of mannose (eg, α-1,6-mannose). These components are cross-linked to from a multilayered cell wall matrix. In addition, other polysaccharides may be unique to specific fungal species and therefore useful for identification. During infection, fungal cell walls exert important pathobiological properties. The surface components of the cell wall mediate attachment of the fungus to host cells. Specific fungal cell wall moieties bind to pattern recognition receptors on host cell membranes, such as certain Toll-like receptors, to stimulate innate immune responses. Cell wall glucans and other polysaccharides may activate the complement cascade and provoke an inflammatory reaction. Most of these polysaccharides are poorly degraded by the host and can be detected with special histologic stains. Cell walls also release immunodominant antigens that may elicit cellular immune responses and diagnostic antibodies. In addition, some yeasts and molds are described as dematiaceous because their cell walls contain melanin, which imparts a brown or black pigment to the fungal colony. Several studies have shown that melanin protects these fungi from host defenses.
Taxonomy
Fungi were initially classified into phyla based largely on their modes of sexual reproduction and phenotypic data. These methods have been supplanted by molecular systematics, which more accurately reflect phylogenetic relationships. There is some ambiguity about the divergence of fungi and animals and their extant ancestors. The lower fungi were assigned to the Phylum Zygomycota, but this phylum was shown to be polyphyletic and has been replaced by the Phylum Glomerulomycota, four subphyla and two zoopathogenic Orders, the Mucorales and the Entomophthorales. However, the two largest phyla, Ascomycota and Basidiomycota, are well supported by phylogenetic analyses. All three of these phyla contain yeasts, molds, and dimorphic species. The Phylum Ascomycota (or ascomycetes) includes more than 60% of the known fungi and about 85% of the human pathogens. Most of the other pathogenic fungi are members of the Phylum Basidiomycota (basidiomycetes) or the Order Mucorales. These medically relevant taxa are distinguished by their modes of reproduction. Sexual reproduction typically occurs when mating-compatible strains of a species are stimulated by pheromones to undergo plasmogamy, karyogamy (nuclear fusion), and meiosis, resulting in the exchange of genetic information and the formation of haploid sexual spores.
For molds within the Order Mucorales, the vegetative hyphae have few septations, the product of sexual reproduction between mating-compatible isolates is a zygospore, and asexual reproduction occurs via sporangia, which are borne on aerial sporangiophores (see Glossary). Examples include species of Rhizopus, Lichtheimia, and Cunninghamella. Among the ascomycetes, sexual reproduction usually requires the fusion of mating-compatible strains and involves the formation of a sac or ascus in which karyogamy and meiosis occur, producing haploid ascospores. They reproduce asexually with the pro duction of conidia. Ascomycetous molds have septate hyphae. Most pathogenic yeasts (Candida and Saccharomyces) and molds (Coccidioides, Blastomyces, and Trichophyton) are ascomycetes. The basidiomycetes include mushrooms as well as pathogenic species of Cryptococcus, Malassezia, Trichosporon, and others. Sexual reproduction results in dikaryotic hyphae and four progeny basidiospores that are supported by a club shaped basidium. In the diagnostic laboratory, multiple approaches are deployed to identify clinical isolates, including molecular and phenotypic features (eg, signature DNA sequences, morphology of reproductive structures, and physiologic properties). Clinical isolates almost always represent infection by a single clone and reproduce asexually in the laboratory. Consequently, many pathogens were initially classified according to their asexual reproductive structures or anamorphic states, and with the subsequent discovery of a sexual cycle, such taxa acquired a teleomorphic name. During the evolution to become successful pathogens, some fungi have apparently lost the ability to reproduce sexually.
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