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2.
To emphasize the eukaryotic nature of the fungi and its relationship to
pathogenesis.
3. To establish familiarity with the scientific terminology peculiar to mycology.
4. To explore the nature of the pathogenesis of fungal infections.
5. To gain familiarity with the classification of medically-important fungi.
6.
To develop an understanding of the nature and mode of action of anti-fungal
agents.
Fungi can be divided into two basic morphological forms, yeasts and hyphae. Yeastsare unicellular fungi which reproduce asexually by blastoconidia formation (budding) or fission. Hyphaeare multi-cellular fungi which reproduce asexually and/or sexually. Dimorphism is the condition where by a fungus can exhibit either the yeast form or the hyphal form, depending on growth conditions. Very few fungi exhibit dimorphism. Most fungi occur in the hyphae form as branching, threadlike tubular filaments. These filamentous structures either lack cross walls (coenocytic) or have cross walls (septate) depending on the species. In some cases septate hyphae develop clamp connections at the septa which connect the hyphal elements.
A.
Yeast cells reproducing by blastoconidia formation; B. Yeast dividing by
fission; C. Pseudohyphal development; D. Coenocytic hyphae; E. Septate
hyphae; F. Septate hyphae with clamp connections
From
Medical
Microbiology, 1990, Murray, et al., p. 299, Fig. 28-1. Reproduced with
permission.
A mass of hyphal elements is termed the mycelium (synonymous with mold). Aerial hyphae often produce asexual reproduction propagules termed conidia(synonymous with spores). Relatively large and complex conidia are termed macroconidia while the smaller and more simple conidia are termed microconidia. When the conidia are enclosed in a sac (the sporangium), they are called endospores. The presence/absence of conidia and their size, shape and location are major features used in the laboratory to identify the species of fungus in clinical specimens.
A. Aspergillus; B. Penicillium; C. Geotrichum; D. Trichophyton; E. Microsporum; F. Epidermophyton and G. Rhizopus. From Medical Microbiology, 1990, Murray, et al., p. 300, Fig. 28-2. Reproduced with permission.
Asexual reproduction, via conidia formation, does not involve genetic recombination between two sexual types whereas sexual reproduction does involve genetic recombination between two sexual types.
1.
The synthesis of chitin, a polymer of N-acetyl glucosamine, and other
compounds, for use in forming the cell wall. These induce immune
hypersensitivity.
2.
The synthesis of ergosterol for incorporation into the plasma membrane.
This
makes the plasma membrane sensitive to those antimicrobial agents which
either block the synthesis of ergosterol or prevent its incorporation into
the
membrane or bind to it, e.g. amphotericin B.
3. The synthesis of toxins such as
a. Ergot alkaloids-
these are produced by Claviceps purpurea and
cause an alpha adrenergic blockade
b. Psychotropic agents - these include psilocybin, psilocin
and lysergic acid
diethylamide (LSD)
c. Aflatoxins
- these are carcinogens produced by Aspergillus flavus
when growing on grain. When these grains are eaten by humans or
when they are fed to dairy cattle and they get into the milk supply, they
affect humans.
4.
The synthesis of proteins on ribosomes that are different from those found
in
bacteria. This makes the fungi immune to those antimicrobial agents that
are
directed against the bacterial ribosome, e.g., chloramphenicol.
5.
The ability of certain metabolites to alter morphology of yeast and/or
be
assimilated by yeast with concomitant clinical identification affects.
2. Positive stain with
3. Negative stain with India inkC. Culture of fungi on
2. Mycosel
agar (selective for pathogenic fungi because of
chloramphenicol and cycloheximide in medium)
2.
Cellular morphology
2. Behavior in broth and serum (germ tube formation)
3. Behavior on cornmeal agar (pseudohyphae formation)
Fatty acid content
of the skin
pH of the skin, mucosal
surfaces and body fluids
Epithelial turnover
Normal flora
Transferrin
Cilia of respiratory
tract
When fungi do pass the resistance barriers of the human body and establish infections, the infections are classified according to the tissue levels initially colonized.
A. Superficial
mycoses - infections limited to the outermost layers of the
skin
and hair. The superficial mycoses are:
B. Cutaneous
mycoses - infections that extend deeper into the epidermis,
as
well as invasive hair and nail diseases.
These diseases are
restricted to the keratinized layers of the skin, hair and nails. Unlike
the superficial mycoses, various cellular immune responses may be evoked,
causing pathologic changes in the host that may be expressed in the deeper
layers of the skin. The agents causing these diseases are termed dermatophytes.
The diseases are referred to as ringwormor tinea.
All of the dermatophytic diseases are caused by members of three genera,
Microsporum,
Trichophyton and Epidermophyton, which comprise 41 species.
The cutaneous mycoses are:
C. Subcutaneous
mycoses - infections involving the dermis, subcutaneous
tissues, muscle and fascia
These infections initially involve the deeper layers of the dermis,
subcutaneous tissue or bone. Most infections have a chronic or insidious
growth pattern, eventually extending into the epidermis and are expressed
clinically as lesions on the skin surface. They are initiated by trauma
to the
skin and are difficult to treat and surgical intervention (excision or
amputation)
is frequently employed. The subcutaneous mycoses are:
D. Systemic
mycoses - infections that originate primarily in the lung
and may
spread to many organ systems.
Unlike most other fungi, the five systemic mycotic agents are inherently
virulent. Each species has biochemical and structural features that enable
it to
evade host defenses. The primary focus of infection is the lung but secondary
infection may occur elsewhere in the body. The five etiological agents
are
identified by their morphology on agar plates (saprobic phase) and in tissue
(parasitic phase):
Dimorphic with mold to yeast transition when infecting susceptible species.
Yeast cells are relatively small. Saprobic phase shows tuberculate
macroconidia.
Dimorphic with mold to yeast transition when infecting susceptible species.
Yeast cells are medium size with thick walls.
Dimorphic with mold to yeast transition when infecting susceptible species.
Yeast cells have multiple buds.
Dimorphic with mold to spherule
transition when infecting susceptible
species. Spherules are multinucleate.
Monomorphic with yeast phase only. This is the only pathogenic yeast with
a
capsule. The capsule is extremely large.
E. Opportunistic
mycoses - infections in patients with immune deficiencies
who would otherwise not be infected
Opportunistic mycoses are seen in those people with impaired host
defenses such as occurs in
The major opportunistic
mycoses include:
Nystatin - binds to ergosterol and disrupts plasma membrane. Highly insoluble and toxic and therefore used topically only.
Terbinafine - Binds to and inhibits squalene epoxidase which blocks ergosterol synthesis.
Haloprogin - a halogenated phenolic ether administered topically for dermatophytic infections.
Ciclopirox olamine - a topical for the treatment of dermatophytic infections and Candida albicans.
Tolnaftate - a thiocarbonate used to treat dermatophytic infections.
Potassium iodide (KI) - Given orally for sporotrichosis
2.
Hyphae are branching, threadlike, tubular filaments that either lack cross
walls
(coenocytic) or have cross walls (septate).
3.
Hyphae reproduce asexually via the formation of spores termed microconidia
or macroconidia.
4.
Fungi produce toxins such as ergot alkaloids, psychotropic agents and
aflatoxins.
5.
Visualization of fungi in human tissue is accomplished by treatment with
10%
KOH and staining with lactophenol cotton blue, Grocott silver stain,
hematoxylin or eosin.
6. India ink may be used as a negative stain to emphasize the capsule of yeast.
7.
The physician can use an ultraviolet lamp (Wood's lamp) to detect fluorescent
compounds produced by fungi growing in or on human tissue.
8.
Fungal diseases are classified according to their depth of penetration
of human
tissue. Thus, there are the superficial mycoses, cutaneous mycoses,
subcutaneous mycoses and systemic mycoses.
9.
The superficial mycoses include pityriasis versicolor, tinea nigra, black
piedra
and white piedra.
10.
The cutaneous mycoses (tineas or ringworms) are restricted to growth in
the
keratinized layers of the skin, hair and nails.
11.
The subcutaneous mycoses penetrate the dermis, subcutaneous tissue,
muscle and fascia. These include sporotrichosis, chromoblastomycosis and
mycetoma.
12.
Systemic mycoses originate in the lung and then may spread to many organ
systems. These include histoplasmosis, North American blastomycosis, South
American blastomycosis, coccidioidomycosis and fungal meningitis.
13. Fungi are most commonly cultured on Sabouraud's agar or Mycosel agar.
14.
Opportunistic mycoses are often secondary to other diseases that
compromise host immunity such as AIDS, diabetes, and malignancy.
15.
Antifungal agents are classified according to their chemical structure
as
macrolides, azoles, allylamines, pyrimidine analogs and miscellaneous.
16.
The polyene antifungals are amphotericin B and nystatin which bind to
ergosterol in the plasma membrane, thus disrupting it.
17.
The azole antifungals include fluconazole and ketoconazole plus numerous
others. They all block ergosterol synthesis by binding to cytochrome P-450.
18.
The allylamines include naftifine and terbinafine which inhibit squalene
epoxidase, thus blocking ergosterol synthesis.
19.
The pyrimidine analogs such as flucytosine incorporate into RNA and/or
DNA thus blocking protein synthesis or DNA synthesis.
20.
The miscellaneous antifungals include griseofulvin, haloprogin, ciclopirox
olamine, tolnaftate and potassium iodide.
21.
The three genera of dermatophytes are Microsporum, Trichophyton
and
Epidermophyton.
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