mycetomas , etc.
| INTRODUCTION TO MYCOLOGY -
© Dr Dennis
Kunkel (used with permission)
information can be
are eukaryotic organisms that do not contain chlorophyll, but have
cell walls, filamentous structures, and produce spores. These
organisms grow as saprophytes and decompose dead organic matter.
There are between 100,000 to 200,000 species depending on how they
are classified. About 300 species are presently known to be
pathogenic for man.
There are four types of
1. Hypersensitivity - an allergic reaction to molds and spores.
2. Mycotoxicoses - poisoning of man and animals by feeds and food
products contaminated by fungi which produce toxins from the grain
3. Mycetismus- the ingestion of preformed toxin (mushroom
In this section, we shall be concerned only with the last type.
INTRODUCTION TO MYCOLOGY
Dr. Arthur Di
650/720) Lecture 88
eukaryotic organisms that do not contain chlorophyll, but have cell
walls, filamentous structures, and produce spores. These organisms
grow as saprophytes and decompose dead organic matter. There are
between 100,000 to 200,000 species depending on how they are
classified. About 300 species are presently known to be pathogenic
There are five
kingdoms of living things. The fungi are in the Kingdom Fungi.
characteristic is responsible for the therapeutic dilemma in anti-mycotic
The taxonomy of
the Kingdom Fungi is evolving and is controversial. Formerly based
on gross and light microscopic morphology, studies of ultra
structure, biochemistry and molecular biology provide new evidence
on which to base taxonomic positions. Medically important fungi are
in four phyla:
1. Ascomycota -
Sexual reproduction in a sack called an ascus with the production of
-Sexual reproduction in a sack called a basidium with the production of
3. Zygomycota -
sexual reproduction by gametes and asexual reproduction with the
formation of zygospores.
4. Mitosporic Fungi
(Fungi Imperfecti) - no recognizable form of sexual reproduction.
Includes most pathogenic fungi.
Pathogenic fungi can
exist as yeasts or as hyphae. A mass of hyphae is called mycelia. Yeasts
are unicellular organisms and mycelia are multicellular filamentous
structures, constituted by tubular cells with cell walls. The yeasts
reproduce by budding. The mycelial forms branch and the pattern of
branching is an aid to the morphological identification. If the mycelia
do not have SEPTA, they are called coenocytic (nonseptate). The terms
"hypha" and "mycelium" are frequently used
interchangeably. Some fungi occur in both the yeast and mycelial forms.
These are called dimorphic fungi.
The dimorphic fungi
have two forms:
1. YEAST -
(parasitic or pathogenic form). This is the form usually seen in tissue,
in exudates, or if cultured in an incubator at 37 degrees C.
2. MYCELIUM -
(saprophytic form). The form observed in nature or when cultured at 25
degrees C. Conversion to the yeast form appears to be essential for
pathogenicity. In the dimorphic fungi. Fungi are identified by several
morphological or biochemical characteristics, including the appearance
of their fruiting bodies. The asexual spores may be large (macroconidia,
chlamydospores) or small (microconidia, blastospores, arthroconidia).
There are four types
of mycotic diseases:
- an allergic reaction to molds and spores.
2. Mycotoxicoses -
poisoning of man and animals by feeds and food products contaminated by
fungi which produce toxins from the grain substrate.
3. Mycetismus- the
ingestion of toxin (mushroom poisoning).
We shall be
concerned only with the last type; pathogenic fungi which cause
infections. Most common pathogenic fungi do not produce toxins but they
do show physiologic modifications during a parasitic infection (e.g.,
increased metabolic rate, modified metabolic pathways and modified cell
wall structure). The mechanisms which cause these modifications as well
as their significance as a pathogenic mechanism are just being
described. Most pathogenic fungi are also thermotolerant, and can resist
the effects of the active oxygen radicals released during the
respiratory burst of phagocytes. Thus, fungi are able to withstand many
host defenses. Fungi are ubiquitous in nature and most people are
exposed to them. The establishment of a mycotic infection usually
depends on the size of the inoculum and on the resistance of the host.
The severity of the infection seems to depend mostly on the immunologic
status of the host. Thus, the demonstration of fungi, for example, in
blood drawn from an intravenous catheter can correspond to colonization
of the catheter, to transient fungemia (i.e., dissemination of fungi
through the blood stream), or to a true infection. The physician must
decide which is the clinical status of the patient based on clinical
parameters, general status of the patient, laboratory results, etc. The
decision is not trivial, since treatment of systemic fungal infections
requires the aggressive use of drugs with considerable toxicity. Most
mycotic agents are soil saprophytes and mycotic diseases are generally
not communicable from person-to-person (occasional exceptions: Candida
and some dermatophytes). Outbreaks of disease may occur, but these are
due to a common environmental exposure, not communicability. Most of the
fungi which cause systemic infections have a peculiar, characteristic
ecologic niche in nature. This habitat is specific for several fungi
which will be discussed later. In this environment, the normally
saprophytic organisms proliferate and develop. This habitat is also the
source of fungal elements and/or spores, where man and animals,
incidental hosts, are exposed to the infectious particles. It is
important to be aware of these associations to diagnose mycotic
diseases. The physician must be able to elicit a complete history from
the patient including occupation, avocation and travel history. This
information is frequently required to raise, or confirm, your
differential diagnosis. The incidence of mycotic infections is currently
increasing dramatically, due to an increased population of susceptibles.
Examples are patients with AIDS, patients on immunosuppressive therapy,
and the use of more invasive diagnostic and surgical procedures
(prosthetic implants). Fungal diseases are non-contagious and
non-reportable diseases in the national public health statistics.
However, in South Carolina most of the important mycotic (fungal)
diseases were notifiable to the public health authorities until 1994.
1. Skin scrapings
suspected to contain dermatophytes or pus from a lesion can be mounted
in KOH on a slide and examined directly under the microscope.
2. Skin testing
(dermal hypersensitivity) used to be popular as a diagnostic tool, but
this use is now discouraged because the skin test may interfere with
serological studies, by causing false positive results. It may still be
used to evaluate the patient's immunity, as well as a population
exposure index in epidemiological studies.
3. Serology may be
helpful when it is applied to a specific fungal disease; there are no
screening antigens for 'fungi' in general. Because fungi are poor
antigens, the efficacy of serology varies with different fungal
infections. The serologic tests will be discussed under each mycosis.
The most common serological tests for fungi are based on latex
agglutination, double immunodiffusion, complement fixation and enzyme
immunoassays. While latex agglutination may favor the detection of IgM
antibodies, double immunodiffusion and complement fixation usually
detect IgG antibodies. Some EIA tests are being developed to detect both
IgG and IgM antibodies. There are some tests which can detect specific
fungal antigens, but they are just coming into general use.
fluorescent microscopy may be used for identification, even on
non-viable cultures or on fixed tissue sections. The reagents for this
test are difficult to obtain.
5. Biopsy and
histopathology. A biopsy may be very useful for the identification
and as a source of the of tissue-invading fungi. Usually the Gomori
methenamine silver (GMS) stain is used to reveal the organisms which
stain black against a green background. The H&E stain does not
always tint the organism, but it will stain the inflammatory cells.
6. Culture. A
definitive diagnosis requires a culture and identification. Pathogenic
fungi are usually grown on Sabouraud dextrose agar. It has a slightly
acidic pH (~5.6); cyclohexamide, penicillin, streptomycin or other
inhibitory antibiotics are often added to prevent bacterial
contamination and overgrowth. Two cultures are inoculated and incubated
separately at 25 degrees C and 37 degrees C to reveal dimorphism. The
cultures are examined macroscopically and microscopically. They are not
considered negative for growth until after 4 weeks of incubation.
Mammalian cells do
not contain the enzymes which will degrade the cell wall polysaccharides
of fungi. Therefore, these pathogens are difficult to eradicate by the
animal host defense mechanisms. Because mammals and fungi are both
eukaryotic, the cellular milieu is biochemically similar in both. The
cell membranes of all eukaryotic cells contain sterols; ergosterol in
the fungal cell membrane and cholesterol in the mammalian cell membrane.
Thus, most substances which may impair the invading fungus will usually
have serious side effects on the host. Although one of the first
chemotherapeutic agents (oral iodides) was an anti-mycotic used in 1903,
the further development of such agents has been left far behind the
development of anti-bacterial agents. The selective toxicity necessary
to inhibit the invading organism with minimal damage to the host has
been difficult to establish within eukaryotic cells.
antifungal agents are:
antimycotic. It is usually the drug of choice for most systemic fungal
infections. It has a greater affinity for ergosterol in the cell
membranes of fungi than for the cholesterol in the host's cells; once
bound to ergosterol, it causes disruption of the cell membrane and death
of the fungal cell. Amphotericin B is usually administered intravenously
(patient usually needs to be hospitalized), often for 2-3 months. The
drug is rather toxic; thrombo-phlebitis, nephrotoxicity, fever, chills
and anemia frequently occur during administration.
The azoles (imidazoles
and triazoles), including ketoconazole, fluconazole, and itraconozole,
are being used for muco-cutaneous candidiasis, dermatophytosis, and for
some systemic fungal infections. Fluconazole is presently essential for
the maintenance of AIDS patients with cryptococcosis. The general
mechanism of action of the azoles is the inhibition of ergosterol
synthesis. Oral administration and reduced toxicity are distinct
Griseofulvin is a
very slow-acting drug which is used for severe skin and nail infections.
Its effect depends on its accumulation in the stratum corneum where it
is incorporated into the tissue and forms a barrier which stops further
fungal penetration and growth. It is administered orally. The exact
mechanism of action is unknown.
or 5-FC) inhibits RNA synthesis and has found its main application in
cryptococcosis (to be discussed later). It is administered p.o.
CLASSIFICATION OF THE MYCOSES
Fungal diseases may
be discussed in a variety of ways. The most practical method for medical
students is the clinical taxonomy which divides the fungi into:
mycoses (or cutaneous mycoses) are fungal diseases that are confined to
the outer layers of the skin, nail, or hair, (keratinized layers) rarely
invading the deeper tissue or viscera. The fungi involved are called
dermatophytes. The Subcutaneous mycoses are confined to the subcutaneous
tissue and only rarely spread systemically. They usually form deep,
ulcerated skin lesions or fungating masses, most commonly involving the
lower extremities. The causative organisms are soil saprophytes which
are introduced through trauma to the feet or legs. The Systemic mycoses
may involve deep viscera and become widely disseminated. Each fungus
type has its own predilection for various organs which will be described
as we discuss the individual diseases.
mycoses are infections due to fungi with low inherent virulence. The
etiologic agents are organisms which are common in all environments.