Fungal Classification, Structure, and Replication - Chapter 4 PDF

FUNGAL CLASSIFICATION, STRUCTURE, AND REPLICATION Chapter # 4 IMPORTANCE OF FUNGI  The fungi represent a ubiquitous and diverse group of organisms, main purpose of which is to degrade organic matter.  All fungi lead a heterotrophic existence.  Fungi have emerged in the past 2 decades as...

FUNGAL CLASSIFICATION, STRUCTURE, AND REPLICATION Chapter # 4 IMPORTANCE OF FUNGI  The fungi represent a ubiquitous and diverse group of organisms, main purpose of which is to degrade organic matter.  All fungi lead a heterotrophic existence.  Fungi have emerged in the past 2 decades as major causes of human disease.  The overall incidence of specific invasive mycoses continues to increase with time.  In short, there are no nonpathogenic fungi. FUNGAL TAXONOMY, STRUCTURE AND REPLICATION  They are eukaryotic organisms, distinguished from other eukaryotes by a rigid cell wall composed of chitin and glucan.  Cell membrane in which ergosterol is substituted for cholesterol as the major sterol component.  Classic fungal taxonomy relies heavily on morphology and mode of spore production.  Advent of rapid DNA sequencing has resulted in a revolution in fungal taxonomy.  A species is a group of organisms with matching gene lineages.  Fungi may be unicellular or multicellular.  The simplest way to group fungi is by their shape, classifying them as either yeasts or molds.  Yeast can be defined morphologically as a cell that reproduces by budding or fission.  A progenitor or “mother” cell pinches off a portion of itself to produce a progeny or “daughter” cell.  The daughter cells may elongate to form pseudohyphae.  Yeasts are usually unicellular and produce round, pasty, or mucoid colonies on agar.  On the other hand, molds are multicellular organisms consisting of threadlike tubular structures called hyphae, that elongate at their tips by a process known as apical extension.  Hyphae are either coenocytic (hollow and multinucleate) or septate (divided by walls).  The hyphae form together to produce a mat like structure called a mycelium.  The colonies formed by molds are often described as filamentous, hairy, or woolly.  On agar plate produce two types of hyphae 1. Vegetative hyphae 2. Aerial hyphae  The aerial hyphae may produce specialized structures known as conidia (asexual reproductive elements).  The conidia may be produced either by a blastic (budding) process or splitting (thallic).  The conidia are easily airborne and serve to disseminate the fungus.  The size, shape, and certain developmental features of conidia are used as a means of identifying fungi to genus and species.  Many fungi of medical importance are termed dimorphic because they may exist in both yeast and a mold form. METABOLISM AND GROWTH CHARACTERISTICS  Most fungi exhibit aerobic respiration, although some are facultative anaerobic (fermentative) and others are strictly anaerobic.  Metabolically fungi are heterotrophic and biochemically versatile, producing both primary (e.g., citric acid, ethanol, glycerol) and secondary (e.g., antibiotics [penicillin], amanitins, aflatoxins) metabolites.  Relative to the bacteria, fungi are slow growing, with cell doubling times in terms of hours rather than minutes.  Table 4.1: Medically Important Fungi (Kingdom Fungi) Taxonomic Designation Representative Genera Human Disease Phylum Glomeromycota (Mucormycetes) Order: Mucorales Rhizopus, Mucor, Lichtheimia, Saksenaea Mucormycosis: opportunistic in patients with diabetes, leukemia, severe burns, or malnutrition; rhinocerebral infections Order: Entomophthorales Basidiobolus, Conidiobolus Entomophthoromycosis: subcutaneous and gastrointestinal infections Phylum: Basidiomycota Teleomorphs of Cryptococcus, Malassezia, and Cryptococcosis and numerous mycoses (Basidiomycetes) Trichosporon spp. Phylum: Ascomycota (Ascomycetes) Class: Pneumocystidomycetes Pneumocystis jirovecii Pneumocystis pneumonia Class: Saccharomycetes Teleomorphs of Candida spp.; Saccharomyces Numerous mycoses Class: Eurotiomycetes Arthroderma (teleomorphs of Trichophyton and Dermatophytoses, systemic mycoses Order: Onygenales Microsporum); Ajellomyces (teleomorphs of Blastomyces and Histoplasma spp.) Order: Eurotiales Teleomorphs of Aspergillus spp. Aspergillosis Class: Sordariomycetes Teleomorphs of Fusarium spp. Keratitis and other invasive mycoses Order: Hypocreales Order: Microascales Pseudallescheria (teleomorph of Scedosporium Pneumonia, mycetoma, and invasive spp.) Mycoses Phylum: Microspora Encephalitozoon, Enterocytozoon, Nosema, Keratoconjunctivitis, sinusitis, (Microsporidia) Trachipleistophora pneumonitis, diarrhea, encephalitis, disseminated infection  Fungi reproduce by formation of spores that may be sexual or asexual.  The fungi in the Ascomycota, Basidiomycota, Glomeromycota, and Microspora produce both sexual and asexual spores.  The form of the fungus producing sexual spores is termed the teleomorph, and the form producing asexual spores is termed the anamorph.  The fact that the teleomorph and anamorph of the same fungus have different names (e.g., Ajellomyces capsulatum [teleomorph] and Histoplasma capsulatum [anamorph]) is a source of confusion for non-mycologists. Table 4.2 Biological, Morphologic, and Reproductive Characteristics of Pathogenic Fungi Organism Group Representative Genera Morphology Reproduction Mucormycetes Rhizopus, Mucor, Broad, thin-walled, coenocytic Asexual: production of Lichtheimia, Basidiobolus hyphae, 6-25 μm with nonparallel sporangiospores within sides; spores contained within sporangium. Sexual: production of sporangium; rootlike structures zygospores formed by fusion of called rhizoids characteristic of compatible mating type some genera. Basidiomycetes Anamorphic Budding yeasts, hyphae, and Asexual: production of conidia by basidiomycetous yeasts arthroconidia. Hyphae that produce budding from a mother cell or (Cryptococcus, Malassezia, basidiospores (not seen in nature or within a hyphal fragment. Sexual: Trichosporon) in patients). Hyphae with clamp fusion of compatible nuclei connections followed by meiosis to form basidiospores or not identified Pneumocystidomycetes Pneumocystis jirovecii Trophic forms and cystlike Asexual: binary fission. Sexual: structures fusion of compatible mating types to form zygote; compartmentalization of spores within cyst Saccharomycetes Candida and Budding yeasts and hyphae, Asexual: production of conidia by Saccharomyces pseudohyphae budding from a mother cell. Sexual: either not seen or by conjugation between two single cells or by “mother-bud” conjugation Eurotiomycetes Dermatophytes, Budding yeasts, septate hyphae, Asexual: production of conidia by Blastomyces, Histoplasma, asexual conidia budding from a mother cell. Aspergillus, Fusarium, borne on specialized structures Sexual: ascospores produced in a Scedosporium spp. specialized structure called an ascus or not seen.  In light of this confusion, code of mycologic nomenclature was modified to apply a policy where a given fungus will have only one name.  Any valid name proposed for a species can be its correct name.  At this time it is permissible to refer to a fungus by its asexual designation if that is the form usually obtained in culture.  For example, Histoplasma capsulatum is the anamorph of the ascomycete Ajellomyces capsulatum.  The anamorph is the stage that is most often encountered in culture, and only under special conditions is the sexual stage formed.  Thus the clinical isolate is known as Histoplasma capsulatum.  Asexual spores consist of two general types: sporangiospores and conidia.  Sporangiospores are asexual spores produced in a sporangia and are characteristic of genera belonging to the Mucorales, such as Rhizopus and Mucor spp.  Conidia are asexual spores that are borne naked on specialized structures as seen in Aspergillus spp., Penicillium spp and the dermatophytes. ASCOMYCOTA (ASCOMYCETES)  The phylum contains almost 50% of all named fungal species and accounts for approximately 80% of fungi of medical importance.  Sexual reproduction leads to the development of ascospores, which are produced in a specialized saclike structure known as an ascus.  Asexual reproduction consists of the production of conidia from a generative or conidiogenous cell.  The Ascomycota consists of four classes of medical importance: the Pneumocystidomycetes, Saccharomycetes, Eurotiomycetes, and Sordariomycetes.  The class Pneumocystidomycetes contains the genus Pneumocystis, formerly classified as a protozoan but now reassigned to the Kingdom Fungi on the basis of gene sequence comparisons.  Saccharomycetes contains the ascomycetous yeasts, whereas Eurotiomycetes and Sordariomycetes contain the filamentous ascomycetes. PNEUMOCYSTIDOMYCETES  Pneumocystidomycetes is a new class that was recently described to include an organism, Pneumocystis carinii, formerly considered to be a protozoan.  The reclassification of Pneumocystis was based on molecular evidence that it was most closely related to the ascomycete Schizosaccharomyces pombe.  Further molecular studies resulted in the naming of human-derived strains as Pneumocystis jirovecii.  The organism exists in a vegetative trophic form that reproduces asexually by binary fission.  Fusion of compatible mating types results in a spherical cyst or spore case, which on maturity contains eight spores. SACCHAROMYCETES  The class Saccharomycetes contains the ascomycetous yeasts.  Characterized by vegetative yeast cells that proliferate by budding or fission.  Many members of the order Saccharomycetales have an anamorphic stage belonging to the genus Candida.  This genus consists of approximately 200 anamorphic species, has teleomorphs in more than 10 different genera, including Clavispora, Debaromyces, Issatchenkia, Kluyveromyces, and Pichia. Under the “one fungus one name” concept, many of these will be renamed. EUROTIOMYCETES  In the class Eurotiomycetes, sexual reproduction leads to the formation of a thin- walled sac (ascus) that contains the haploid ascospores.  This class has seven orders that include species pathogenic to humans.  Among the more important are the order Onygenales, which contains the dermatophytes and a number of dimorphic systemic pathogens (including H. capsulatum and Blastomyces dermatitidis).  Order Eurotiales, which contains the teleomorphs of the anamorphic genera Aspergillus and Penicillium. SORDARIOMYCETES  In the class Sordariomycetes, the order Hypocreales contains the teleomorphs of the anamorphic genus Fusarium, and the order Microascales contains the teleomorphs (Pseudallescheria) of the anamorphic genus Scedosporium.  Many medically important melanized (dematiaceous) fungi have teleomorphs in this class. BASIDIOMYCOTA (BASIDIOMYCETES)  Most members of the Basidiomycetes have a separate filamentous form, but some are typical yeasts.  Sexual reproduction leads to the formation of haploid basidiospores on the outside of a generative cell termed a basidium.  The most prominent human pathogens in the phylum Basidiomycetes are the basidiomycetous yeasts with anamorphic stages belonging to the genera Cryptococcus, Malassezia, and Trichosporon.  The genus Cryptococcus, which contains more than 30 different species, has teleomorphs (sexual stages) that have been assigned to the genera Filobasidium and Filobasidiella.  The filamentous basidiomycetes are increasingly recognized as causes of opportunistic fungal infections.  In culture these organisms often produce fast-growing, sterile, white colonies with clamp connections hyphal outgrowths that form a bypass around the septum to facilitate the migration of a nucleus.  Most filamentous basidiomycetes are wood- rotting fungi, the most frequently reported cause of human infection is Schizophylum commune. GLOMEROMYCOTA  Include molds with broad, sparsely septate, coenocytic hyphae.  The subphylum Mucoromycotina has been proposed to accommodate the Mucorales, and the subphylum Entomophthoromycotina includes the Entomophthorales.  These fungi produce sexual zygospores after the fusion of two compatible mating types.  The asexual spores of the order Mucorales are contained within a sporangium (sporangiospores).  The sporangia are borne at the tips of stalk like sporangiophores that terminate in a bulbous swelling called the columella.  The presence of root like structures called rhizoids is helpful in identifying specific genera within the Mucorales.  The order Mucorales is the most clinically important and includes the genera Lichtheimia (formerly Absidia), Mucor, Rhizopus, and Rhizomucor.  The other order, Entomophthorales, is less common and includes the genera Basidiobolus and Conidiobolus.  These organisms cause tropical subcutaneous mucormycosis.  The asexual spores are borne singly on short sporophores and are forcibly ejected when mature. MICROSPORA (MICROSPORIDIA)  Obligate intracellular, unicellular, spore-forming eukaryotes.  Previously categorized as protists, now consider as fungi on the basis of genetic studies.  Structural features of the organisms, such as the presence of chitin in the spore wall, diplokaryotic nuclei, and electron- dense spindle plaques associated with the nuclear envelope, suggest a possible relationship between fungi and microsporidia.  Life cycle of microsporidia is unique.  More than 160 microsporidial genera and 1300 species that are pathogenic in every major animal group have been identified.  Presently, human infections have been shown to involve nine different genera (Anncaliia, Encephalitozoon, Endoreticulatus, Enterocytozoon, Nosema, Pleistophora, Vittaforma, Tubulinosema, and Trachipleistophora) as well as unclassified microsporidia that have been assigned to the collective group Microsporidium. CLASSIFICATION OF HUMAN MYCOSES  Classification of Human Mycoses  In addition to the formal taxonomic classification of fungi, fungal infections may be classified according to the tissues infected as well as by specific characteristics of organism groups.  These classifications include 1. Superficial 2. Cutaneous 3. Subcutaneous mycoses 4. Endemic mycoses 5. Opportunistic mycoses SUPERFICIAL MYCOSES  Superficial mycoses are those infections that are limited to the very superficial surfaces of the skin and hair.  They are nondestructive and of cosmetic importance only.  The clinical infection termed pityriasis versicolor is characterized by discoloration or depigmentation and scaling of the skin.  Tinea nigra refers to brown- or black-pigmented macular patches localized primarily to the palms.  The clinical entities of black and white piedra involve the hair and are characterized by nodules composed of hyphae that encompass the hair shaft.  The fungi associated with these superficial infections include Malassezia furfur, Hortae werneckii, Piedraia hortae, and Trichosporon spp. CUTANEOUS MYCOSES  Cutaneous mycoses are infections of the keratinized layer of skin, hair, and nails.  These infections may elicit a host response and become symptomatic.  Signs and symptoms include itching, scaling, broken hairs, ringlike patches of the skin, and thickened discolored nails.  The Dermatophytes are fungi classified in the genera Trichophyton, Epidermophyton, and Microsporum.  Infections of the skin involving these organisms are called dermatophytoses.  Tinea unguium refers to infections of the toes involving these agents.  Onychomycosis includes infections of the nails caused by the dermatophytes as well as nondermatophytic fungi (e.g., Candida and Aspergillus spp.). SUBCUTANEOUS MYCOSES  Subcutaneous mycoses involve the deeper layers of the skin and are caused by a broad spectrum of taxonomically diverse fungi.  The fungi gain access to the deeper tissues usually by traumatic inoculation and remain localized, causing abscess formation, nonhealing ulcers, and draining sinus tracts.  The host immune system recognizes the fungi, resulting in variable tissue destruction and frequently epitheliomatous hyperplasia.  Infections may be caused by hyaline molds, such as Acremonium spp. and Fusarium spp., and by pigmented or dematiaceous fungi, such as Alternaria spp., Cladosporium spp. and Exophiala spp. (phaeohyphomycoses, chromoblastomycoses).  Subcutaneous mycoses tend to remain localized and rarely disseminate systemically. ENDEMIC MYCOSES  The endemic mycoses are fungal infections caused by the classic dimorphic fungal pathogens H. capsulatum, B. dermatitidis, Emmonsia pasteuriana, Coccidioides immitis, Coccidioides posadasii, Paracoccidioides brasiliensis, and Talaromyces (Penicillium) marneffei.  These fungi exhibit thermal dimorphism.  Generally confined to geographic regions where they occupy specific environmental or ecologic niches.  The endemic mycoses are often referred to as systemic mycoses.  All of these agents produce a primary infection in the lung, with subsequent dissemination to other organs and tissues. OPPORTUNISTIC MYCOSES  The opportunistic mycoses are infections attributable to fungi that are normally found as human commensals or in the environment.  With the exception of Cryptococcus neoformans and Cryptococcus gattii, these organisms exhibit inherently low or limited virulence and cause infection in individuals who are debilitated, immunosuppressed, or who carry implanted prosthetic devices or vascular catheters.  Virtually any fungus can serve as an opportunistic pathogen.  The most common opportunistic fungal pathogens are the yeasts Candida spp. and C. neoformans, the mold Aspergillus spp., and P. jirovecii. Because of its inherent virulence.  C. neoformans is often considered a “systemic” pathogen. Although this fungus may cause infection in immunologically normal individuals, it clearly is seen more frequently as an opportunistic pathogen in the immunocompromised population.