The Fungi ubiquitous and diverse group of organisms degrade organic matter. heterotrophic existence as saprobes (organisms that live on dead or decaying matter), symbionts (organisms that live together and in which the association is of mutual advantage), commensals (organisms living in a close relationship in which one benefits from the relationship and the other neither benefits nor is harmed), or as parasites (organisms that live on or within a host, from which they derive benefits without making any useful contribution in return; in the case of pathogens the relationship is harmful to the host).
More on Fungi Can be major causes of human disease –Among immunocompromised –Among hospitalized with serious underlying diseases. Fungi are opportunistic pathogens with high morbidity and mortality. Overall incidence of specific invasive mycoses continues to increase with time (Table 7-1) The list of opportunistic fungal pathogens likewise increases each year. In short, there are no nonpathogenic fungi!
Fungal Infections This increase in fungal infections can be attributed to the ever-growing number of immunocompromised patients, –including transplant patients, individuals with acquired immune deficiency syndrome (AIDS), –patients with cancer and who are undergoing chemotherapy, –individuals who are hospitalized with other serious underlying conditions and who undergo a variety of invasive procedures.
Disease Causing Fungi Table 7-1. Candida species Cryptococcus neoformans Coccidioides immitis Aspergillus species Histoplasma capsulatum Agents of Zygomycosis Agents of Hyalohyphomycosis Agents of Phaeohyphomycosis Sporothrix schenckii Malassezia furfur
Fungi Life Style aerobic respiration some are facultatively anaerobic (fermentative) others are strict anaerobes. fungi are heterotrophic and biochemically versatile, producing both primary (e.g., citric acid, ethanol, glycerol) and secondary (e.g., antibiotics [penicillin], amanitens, aflatoxins) metabolites. Relative to the bacteria, fungi are slow growing with cell-doubling times in terms of hours rather than minutes.
Classifying Fungi Five major classes of fungi of medical importance is shown in Table 7-3 Only approximately 200 are known to cause human disease, (Deuteromycetes) although this number appears to be increasing. Reproduce by the formation of spores, which may be sexual (involving meiosis, preceded by fusion of the protoplasm and nuclei of two compatible mating types) or asexual (involving mitosis only). Classes Zygomycetes, Ascomycetes, Archiascomycetes, and Basidiomycetes –produce both sexual and asexual spores -Table 7-4 –The form of the fungus producing sexual spores is termed the teleomorph, – 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 nonmycologists.
More Classification morphology and mode of spore production; ultrastructural features, biochemical and molecular characteristics, Fungi may be unicellular or multicellular. The simplest grouping =yeasts or moulds.
Yeast vs Mold Yeast –reproduces by budding or by fission "mother" cell pinches off a portion of itself to produce "daughter" cell. –The daughter cells may elongate to form sausagelike pseudohyphae. Yeasts are usually unicellular and produce round, pasty, or mucoid colonies on agar.
Molds Moulds –multicellular organisms –Have 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 partitions or cross-walls) (see Figure 7-2).Figure 7-2 The hyphae form together to produce a matlike structure called a mycelium. The colonies formed by moulds are often described as filamentous, hairy, or woolly. –On or beneath the surface hyphae, termed vegetative hyphae, –hyphae that project above the surface of the medium, so-called aerial hyphae. The aerial hyphae may produce specialized structures known as conidia (asexual reproductive elements 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 of the fact that they may exist in both a yeast form and a mould form.
Asexual Spores Asexual spores consist of two general types: –sporangiospores asexual spores produced in a containing structure or sporangium Sporangiospores are characteristic of genera belonging to the class Zygomycetes, –Rhizopus –Mucor spp. –conidia. Conidia are asexual spores that are borne naked on specialized structures, –Aspergillus spp, –Penicillium spp., –dermatophytes.
Four Other Groups of Fungi Ascomycetes Basidiomycetes Zygomycetes Archiascomycetes
ZYGOMYCETES Moulds broad, sparsely septate, coenocytic hyphae. Produce sexual zygospores following 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 stalklike sporangiophores that terminate in a bulbous swelling called the columella The presence of rootlike structures, called rhizoids, is helpful in identifying specific genera within the Mucorales. Most Zygomycetes encountered clinically belong to the order Mucorales. The other order, the Entomophthorales, are less common and include the genera, Basidiobolus and Conidiobolus. T These organisms cause tropical subcutaneous zygomycosis. The asexual spores are borne singly on short sporophores and are forcibly ejected when mature.
ASCOMYCETES include both yeasts (Saccharomycetes) and moulds. The hyphae are septate, asexual spores are produced from conidiogenous cells borne on conidiophores. The sexual spore of the Ascomycetes is the ascospore, characterized by its production within a sac or ascus.
ARCHIASCOMYCETES new class that was recently described to include an organism, Pneumocystis carinii, that had formerly been considered 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 jiroveci. 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.
BASIDIOMYCETES rarely encountered clinically The only human pathogen is Filobasidiella neoformans, the sexual form of Cryptococcus neoformans. The sexual spore of the Basidiomycetes is the basidiospore, characterized by the extension from a club-shaped structure, the basidium.
DEUTEROMYCETES includes both yeasts and moulds that share a common lack of a sexual phase Many of the fungi pathogenic to humans are included in this class septate hyphae produce conidia from conidiophores and conidiogenous cells. The yeasts reproduce by budding, and the moulds produce conidia by either a blastic (budding) process or a thallic process, in which hyphal segments fragment into individual cells or arthroconidia. Identification of individual genus and species is based in part on microscopic evaluation of the mode of development of the conidium from the conidiogenous cell.
Disease Causing Fungi The largest group of fungi causing infections in humans, the Deuteromycetes Table 7-4 does not produce known sexual spores. Its important to know sexual nature of fungi because –Irrespective of the ability of a given fungus to produce sexual spores, in clinical situations it is common to refer to the organisms by their asexual designations. –The anamorphic (asexual) state is isolated from clinical specimens –Sexual or teleomorphic phase occurs only under very specialized conditions in the laboratory.
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 the superficial, cutaneous, and subcutaneous mycoses; the endemic mycoses; and the opportunistic mycoses
SUPERFICIAL MYCOSES Infections that are limited to the very superficial surfaces of the skin and hair. Nondestructive and of cosmetic importance only. The clinical infection 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, Phaeoannelomyces (Exophiala) werneckii, Piedraia hortae, and Trichosporon spp.
CUTANEOUS MYCOSES 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. Onychomycoses includes infections of the nails caused by the dermatophytes, as well as nondermatophytic fungi such as Candida spp. and Aspergillus spp.
SUBCUTANEOUS MYCOSES Subcutaneous mycoses involve the deeper layers of the skin, including the cornea, muscle, and connective tissue, 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, often, epitheliomatous hyperplasia. Infections may be caused by hyaline moulds 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 Endemic mycoses are fungal infections caused by the classic dimorphic fungal pathogens Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, and Paracoccidioides brasiliensis. These fungi exhibit thermal dimorphism (i.e., exist as yeast at 37°C and mould at 25°C) and are generally confined to specific geographic regions where they occupy specific environmental or ecologic niches. The endemic mycoses are often referred to as systemic mycoses, because these organisms are true pathogens and can cause infection in healthy individuals. Recently the dimorphic fungus Penicillium marneffei was added to the list of agents causing endemic 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 caused by fungi that are normally found as human commensals or in the environment. With the exception of Cryptococcus neoformans, 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, and the list of those identified as such becomes longer each year. The most common opportunistic fungal pathogens are the yeasts Candida spp. and Cryptococcus neoformans, the mould Aspergillus spp., and Pneumocystis jiroveci. Because of its inherent virulence, Cryptococcus neoformans is often considered a "systemic" pathogen. Although this fungus may cause infection in immunologically normal individuals, it clearly is seen more often as an opportunistic pathogen in the immunocompromised population.