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The size of fungi varies immensely. A single cell without transverse septa may range from bacterial size (2-4 μm) to a macroscopically visible structure. The morphologic forms of growth vary from colonies superficially resembling those of bacteria to some of the most complex, multicellular, colorful, and beautiful structures seen in nature. Mushrooms are an example and can be regarded as a complex organization of cells showing structural differentiation.
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Vary from bacterial size to multicellular mushrooms
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Mycology, the science devoted to the study of fungi, has various terms to describe the morphologic components that comprise these structures. The terms and concepts that must be mastered can be limited by considering only the fungi of medical importance and accepting some simplification.
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Fungi that cause human infections can be broadly divided based on their morphological forms. Yeasts are fungi that primarily grow in a round cellular form. Molds are fungi that primarily grow as filamentous, tube-like structures called hyphae (Figure 42–3A and B). Although it is useful to consider this basic distinction based on cell shape, it is important to remember that some fungi can transition between yeast-like and hyphal morphologies. Often, this plasticity of shape is directly related to pathogenesis since different forms may be better suited for different microenvironments. The yeasts tend to have the simplest cellular forms, reproducing by a process of asexual budding, constriction, and cell separation similar to many bacteria. The newly formed daughter cell is often called a blastoconidium.
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Yeasts produce blastoconidia by budding
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Fungi may also grow through the development of hyphae (singular, hypha), which are tube-like extensions of the cell with thick, parallel walls. As the hyphae extend, they form an intertwined mass called a mycelium. Most molds form hyphal septa (singular, septum), which are cross-walls perpendicular to the cell walls, dividing the hypha into subunit cells (Figure 42–4). The structure of these septa varies among species and may contain pores and incomplete walls that allow movement of nutrients, organelles, and nuclei between adjacent cells. Some species, including some human pathogens, form septae that are very distant from each other. Because their microscopic appearance therefore suggests a single, continuous hyphal cell, these particular species are often called “aseptate” molds. In both septate and aseptate hyphae, multiple nuclei are often present in each cell.
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A portion of the mycelium (vegetative mycelium) usually grows into the medium or organic substrate (eg, soil) and functions like the roots of plants as a collector of nutrients and moisture. The more visible surface growth may assume a fluffy character as the mycelium becomes aerial. The hyphal walls are rigid in order to support this extensive, intertwining network. The aerial hyphae bear the reproductive structures of this class of fungi. These sexual structures are often unique to each species, allowing microbiology laboratories to distinguish among molds based on their morphological features. Some fungi also form pseudohyphae, which are actually elongated yeast cells growing end-to-end. Therefore, pseudohyphae are distinguished from true hyphae by having recurring bud-like constrictions and less rigid cell walls.
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✺ Molds produce septate or aseptate hyphae
✺ Vegetative mycelium acts as a root
✺ Aerial mycelium bears reproductive conidia or spores—the basis for species identification
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Exogenously formed conidia may develop directly from the hyphae or on a special stalk-like structure, the conidiophore (Figure 42–3B). Occasionally, terms such as macroconidia and microconidia are used to indicate the size and complexity of these conidia. Conidia that develop within the hyphae are called either chlamydoconidia or arthroconidia. Chlamydoconidia become larger than the hypha itself; they are round, thick-walled structures that may be borne on the terminal end of the hypha or along its course. Arthroconidia conform more to the shape and size of the hyphal units but are thickened or otherwise differentiated. Arthroconidia may form a series of delicately attached conidia that break off and disseminate when disturbed. Some of the asexual reproductive forms are illustrated in Figure 42–5A–D. The most common sexual spore is termed an ascospore. Four or eight ascospores may be found in a sac-like structure, the ascus.
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✺ Pseudohyphae are elongated yeast-like cells
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Conidia and conidiophore arrangements determine names
Ascospores are borne in ascus sac
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Although many fungi tend to grow as either yeasts or molds, some species can transition between morphological forms depending on environmental conditions. These species are known as dimorphic fungi. Many fungi, including the most common human fungal pathogen Candida albicans, display a striking ability to modify their cellular shape and structure in order to adapt to new environments. These morphological transitions are often very important for the pathogenesis of human infections.
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A distinct group of human pathogens are the thermally dimorphic fungi, shifting from yeast-like to hyphal growth based on temperature. These fungal species tend to grow in the mold form in their environmental reservoir as well as when incubated in culture at ambient temperatures. However, they convert to a yeast-like growth form in the mammalian host or when incubated in culture at 37°C. For most, it is possible to manipulate the culture conditions to demonstrate both yeast and mold phases in vitro. Yeast phase growth requires conditions similar to those of the physiologic in vivo environment, such as 35°C to 37°C incubation and enriched medium. Mold growth requires minimal nutrients and ambient temperatures. Importantly, the conidia produced in the mold phase may be infectious and serve to disseminate the fungus during growth in the environment.
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✺ Growth in yeast or mold form
✺ Temperature triggers shift between phases
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The morphologic and physiologic events associated with the temperature-dependent conversion between the mold and yeast phases have been studied in the human pathogen Histoplasma capsulatum. They are understandably complex, given the dramatic change of milieu encountered by the fungus when its mold conidia float from their soil habitat to the pulmonary alveoli. Conversion to the yeast phase is then triggered by the host temperature (37°C) and other conditions associated with the host microenvironment (eg, iron limitation, pH changes, elevated levels of CO2). In vitro studies show that the earliest events in this morphological shift involve induction of the heat shock response and uncoupling of oxidative phosphorylation. These early cellular events are followed by a shutdown of RNA synthesis, protein synthesis, and respiratory metabolism. The cells then pass through a metabolically inactive state, emerging with enhanced enzymatic capacities involving sulfhydryl compounds (eg, cysteine, cystine) that are exclusive to the yeast stage. As yeast growth develops, there is recovery of mitochondrial activity and synthetic capacity, but a new constellation of oxidases, polymerases, proteins, cell wall glucans, and other compounds are present, likely favoring host parasitism. In all, more than 500 genes are differentially expressed in the mold and yeast phases.
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Shift from mold to yeast begins with heat shock response
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✺ Metabolic shift is toward sulfhydryl compounds in yeast form
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Dimorphism in fungi is reversible, a feature that distinguishes it from developmental processes such as embryogenesis seen in higher eukaryotes. The importance of the dimorphism in fungal virulence has been demonstrated in several fungi, including C albicans and H capsulatum. Strains that are locked in one growth phase are markedly reduced in their ability to produce disease and persist in the host.
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✺ Dimorphism is reversible and linked to virulence
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Fungal classification has historically relied upon observable cellular characteristics such as the septation of hyphae and the appearance of the sexual structures. However, DNA sequence-based classification methods are becoming more common, allowing fungi to be grouped by genetic relatedness. Molecular classification techniques have also demonstrated that several microbial species are actually fungi despite having few fungal growth characteristics (eg, Pneumocystis species and Microsporidia).
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✺ Taxonomy is based on sexual spores and septation of hyphae
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rRNA genes are used for classification
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Fungi have historically been organized into five phyla: Ascomycota, Basidiomycota, Zygomycota, Chytridiomycota, and Glomeromycota. The medically important genera fall mostly within the Ascomycota, with a few in Basidiomycota, and Zygomycota, as shown in Table 42–1.
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The grouping of medically important fungi used in the following chapters is based on the types of tissues they parasitize and the diseases they produce, rather than on the principles of basic mycologic taxonomy. The superficial fungi, such as the dermatophytes, cause indolent lesions of the skin and its appendages, commonly known as ringworm and athlete’s foot, without typically spreading to deeper tissues. The subcutaneous pathogens characteristically cause infection through the skin, followed by subcutaneous or lymphatic spread. The opportunistic fungi are those found in the environment or in the resident flora that produce disease primarily in immunocompromised hosts. The systemic pathogens are the most virulent fungi and may cause serious and progressive systemic disease in previously healthy persons. They are not found in the human microbiota. Although their major potential is to produce deep-seated visceral infections and systemic spread (systemic mycoses), they may also produce superficial infections as part of their disease spectrum or as the initiating event. As with all clinical classifications, overlaps and exceptions occur. In the end, the interplay between host and microorganism defines the disease.
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Medical grouping organized by biologic behavior in humans
Systemic fungi infect previously healthy persons