Describe the basic physical characteristics and reproduction of fungi.
Name the fungi of medical importance.
Describe the diseases associated with fungi of medical importance.
Describe the basic methods used to diagnose fungal infections.
Describe the mechanisms of action of the common antifungal drugs.
General Characteristics
Fungi include moulds, yeasts and higher fungi. All fungi are eukaryotic and
have sterols but not peptidoglycan in their cell membrane. They are chemoheterotrophs
(requiring organic nutrition) and most are aerobic. Many fungi are also saprophytes
(living off dead organic matter) in soil and water and acquire their food
by absorption. Characteristically they also produce sexual and asexual spores.
There are over 100,000 species recognised, with 100 infectious agents of man.
Moulds are composed of numerous, microscopic, branching hyphae known collectively
as a mycelium.
Growth occurs from the apical tip, the apical vesicles contain materials
and enzymes for the formation of new hyphal wall. Older hyphae are less biochemically
active and contain many storage vacuoles. In
most moulds these hyphae have septa (crosswalled divisions), but in some
there are none and the hyphae are coenocytic (aseptate).
Septa, (plural of septum) are cross-wall
formations which divide fungal hyphae into cells. They may add strength
to the hyphae or serve to isolate adjacent parts to allow differentiation,
such as during production of the reproductive structures.
The structure of the septa is of taxonomic importance, and may be
simple or complex, septate or aseptate (coenocytic). Growth of a septum
starts at the hyphal wall and proceeds towards the centre of the hyphae,
septa may consist of a solid plate, have a single pore at the centre,
or have multiple pores creating a sieve-like appearance.
Part of the mycelium is involved in gaining nutrients, the vegetative mycelium,
and part in growth and reproduction, the aerial or reproductive mycelium.
From the reproductive mycelium, spores are formed. Asexual spores are produced by the aerial mycelium of a single organism, whereas sexual spores are formed by the fusion of cells and nuclei from opposite mating strains.
There are many types of spore with names such as chlamydospore and sporangiospore. Examples of moulds include Penicillium, the source of penicillin that was the first antibiotic.
Yeasts are unicellular organisms, normally ovoid or spherical in shape. Typically, they replicate by budding rather than binary fission. Here, the cytoplasm and dividing nucleus from the parent is initially a continuum with the bud, or daughter yeast, before a new cell wall is deposited to separate the two. In some cells, these buds fail to detach and may form a short chain of cells called a pseudohypha. Although yeasts are single cells and produce smooth bacterial-like colonies on laboratory agar media, unlike bacteria they have a distinct nucleus and are thus eukaryotes. An example of a yeast is Saccharamyces cerevisiae that produces alcohol under anaerobic fermentation.
Fungal infections or mycoses are classified depending on the degree of tissue involvement and mode of entry into the host. These are:
Superficial - localised to the skin, the hair, and the nails.
Subcutaneous - infection confined to the dermis, subcutaneous tissue or adjacent structures.
Systemic - deep infections of the internal organs.
Opportunistic - cause infection only in the immunocompromised.
Human fungal infections in the United Kingdom are uncommon in normally healthy persons, being confined to conditions such as candidiasis (thrush) and dermatophyte skin infections such as athlete's foot. However, in the immunocompromised host, a variety of normally mild or nonpathogenic fungi can cause potentially fatal infections. Furthermore, the relative ease with which people can now visit "exotic" countries provides the means for unusual fungal infections to be imported into this country.
Superficial Mycoses
As listed above, in superficial mycoses infection is localised to the skin, the hair, and the nails. An example is "ringworm" or "tinea", an infection of the skin by a dermatophyte. Ringworm refers to the characteristic central clearing that often occurs in dermatophyte infections of the skin. Dermatophyte members of the genera Trycophyton, Microsporum and Epidermophyton are responsible for the disease. Tinea can infect various sites of the body, including the scalp (tinea capitis), the beard (tinea barbae) the foot (tinea pedis: "athlete's foot") and the groin (tinea cruris). All occur in the United Kingdom although tinea infections, other than pedis, are now rare.
Candida albicans is a yeast causing candidiasis or "thrush" in humans. As a superficial mycoses, candidiasis typically infects the mouth or vagina. C. albicans is part of the normal flora of the vagina and gastrointestinal tract and is termed a "commensal". However, during times of ill health or impaired immunity the balance can alter and the organism multiplies to cause disease. Antibiotic treatment can also alter the normal bacterial flora allowing C. albicans to flourish.
Subcutaneous Mycoses
These are infections confined to the dermis, subcutaneous tissue or adjacent structures. Infection may arise following the wounding of the skin and the introduction of vegetable matter. These mycoses are rare and confined mainly to tropical regions. They tend to be slow in onset and chronic in duration. An example is sporotrichosis caused by Sporothrix schenckii. The fungus is dimorphic, being a mould that can convert to a yeast form at 37°C on rich laboratory media or in infection. Sporotrichosis was once common in Europe but cases are now rare. The disease is most prevalent the Americas, South Africa and Australia. Infection usually follows and insect bite, thorn prick or scratch from a fish spine. Certain occupation groups appear to have increased risk from infection. These include florists, farm workers and others who handle hay and moss. The most common symptom is a ulcerative lesion that may develop into lymphangitis.
Systemic Mycoses (primary and opportunistic)
These are invasive infections of the internal organs with the organism gaining entry by the lungs, gastrointestinal tract or through intravenous lines. They may be caused by: (i) primary pathogenic fungi or (ii) by opportunistic fungi that are of marginal pathogenicity but can infect the immunocompromised host.
Primary Pathogenic Fungi
Infection occurs in previously healthy persons and arises through the respiratory route. Examples include histoplasmosis, blastomycosis, coccidiomycosis and paracoccidiodomycosis. The fungi occur throughout the world but not in the United Kingdom.
Histoplasmosis. This is caused by Histoplasma capsulatum. The organism is dimorphic (being a mould that can convert to a yeast form). H. capsulatum is endemic in many parts of the world including North and South America. It is found in the soil and growth is enhanced by the presence of bird and bat excreta. Environments containing such material are often implicated as sources of human infection. The lungs are the main site of infection but dissemination to the liver, heart and central nervous system can occur. Pulmonary infection can resemble symptoms seen in tuberculosis.
Opportunistic Fungi
Here, patients usually have some serious immune or metabolic defect, or have undergone surgery. The diseases include aspergillosis, systemic candidosis and cryptococcosis. Exceptionally, other fungi that are normally not pathogenic, such as Trichosporon, Fusarium or Penicillium, may cause systemic infections.
Aspergillosis. This is the name given to a number of different diseases caused by the mould Aspergillus. It produces large numbers of spores and occurs world-wide. In the United Kingdom, A. fumigatus is the most common species causing disease. The organism can infect the lungs, inner ear, sinuses and, rarely, the eye of previously healthy persons. In the immunosuppressed host, Aspergillus can disseminate throughout the body.
Candidosis. In severely immunocompromised patients (e.g. those receiving chemotherapy) C. albicans, that is part of the normal human flora (see above), can proliferate and disseminate throughout the body.
Cryptococcosis. This is a systemic infection caused by the yeast Cryptococcus neoformans. The commonest manifestation is a subacute or chronic form of meningitis resulting from the inhalation of the organism. Pulmonary infection can also occur. The disease affects both healthy and immunosuppressed individuals and occurs world-wide. C. neoformans can be isolated in large numbers from pigeon droppings in the environment, although such birds do not appear to harbour the yeast.
Other Fungal Related Disease
Constant exposure to fungal spores in the atmosphere can induce respiratory allergies. Elevated antibodies to a range of common spore forming fungi have been demonstrated in occupational diseases such as Humidifier fever, Malt workers' lung and Wheat threshers' disease.
Certain fungi, such as mushrooms, can produce poisonous toxins that may prove fatal if ingested (e.g. Amanita phalloides: "death cap"). Others (Psilocybe) affect the central nervous system inducing hallucinogenic responses.
Many moulds produce secondary metabolites (mycotoxins) that are highly toxic to humans. Ergotism is caused by eating bread prepared from rye infected with the fungus Claviceps purpurea. Historically, several large scale outbreaks of madness in local populations have been attributed to ergotism.
Pneumocystis. This is an infection of the lung caused by Pneumocystis carinii. The organism is a common cause of fatal pneumonia in AIDS patients. An intracellular parasite, with a life cycle of trophozoite and cyst, it was formerly considered to be a protozoan. However, comparison of DNA and RNA sequences have established that it is one of the group of ustomycetous red yeast fungi. The cysts contain 8 nuclei which can be seen in smears of pulmonary aspirates. P. carinii is a commensal of many wild and domestic animals and evidence suggests that human infection is commonly derived from dogs.
References
Peters, W. and Gilles, H.M. (1995). Colour Atlas of Tropical Medicine and Parasitology. Mosby-Wolfe.
Roberts, S.O.B., Hay, R.J. and Mackenzie, D.W.R. (1984). A Clinician's Guide to
Fungal Disease. (Infectious Diseases and Antimicrobial agents: 5). Marcel Dekker,
Inc. New York.
