Fungi differ from bacteria in that they have a cell wall composed of chitin rather than peptidoglycan, and a cell membrane containing ergosterol rather than cholesterol. There are two main types of fungi: yeasts, which grow as single cells, and molds, which grow as filaments called hyphae. Many medically important fungi can exist as either molds or yeasts depending on temperature. Fungi reproduce both sexually through spores and asexually through budding or formation of conidia. Host defenses against fungi include intact skin and mucous membranes, as well as cell-mediated immunity and antibodies, though fungi do not produce endotoxins or exotox

1. Fungi/Yeast/Molds
Atifa Ambreen
M. Phil, Microbiology

2. Structure & Growth
 Because fungi (yeasts and molds) are eukaryotic organisms whereas
bacteria are prokaryotic, they differ in several fundamental respects. Two
fungal cell structures are important medically:
 The fungal cell wall consists primarily of chitin (not peptidoglycan as in
bacteria); thus, fungi are insensitive to antibiotics, such as penicillin, that
inhibit peptidoglycan synthesis.
 Chitin is a polysaccharide composed of long chains of N-
acetylglucosamine. The fungal cell wall contains other polysaccharides as
well, the most important of which is -glucan, a long polymer of D-glucose.
The medical importance of -glucan is that it is the site of action of the
antifungal drug caspofungin.
 The fungal cell membrane contains ergosterol, in contrast to the human
cell membrane, which contains cholesterol. The selective action of
amphotericin B and azole drugs, such as fluconazole and ketoconazole,
on fungi is based on this difference in membrane sterols.

4. Types
There are two types of fungi:
1. Yeasts
2. Molds.
1. Yeasts grow as single cells that reproduce by
asexual budding.
2. Molds grow as long filaments (hyphae) and form a
mat (mycelium). Some hyphae form transverse
walls (septate hyphae), whereas others do not
(nonseptate hyphae). Nonseptate hyphae are
multinucleated (coencytic).

6. Important Properties
 Several medically important fungi are thermally
dimorphic; i.e., they form different structures at
different temperatures. They exist as molds in the
environment at ambient temperature and as yeasts (or
other structures) in human tissues at body temperature.
 Most fungi are obligate aerobes; some are facultative
anaerobes; but none are obligate anaerobes. All fungi
require a preformed organic source of carbon—hence
their frequent association with decaying matter. The
natural habitat of most fungi is, therefore, the
environment. An important exception is Candida
albicans, which is part of the normal human flora.

7. Fungal Reproduction
 Some fungi reproduce sexually by
mating and forming sexual spores,
e.g., zygospores, ascospores, and
basidiospores. Zygospores are
single large spores with thick
walls; ascospores are formed in a
sac called ascus; and
basidiospores are formed
externally on the tip of a pedestal
called a basidium. The
classification of these fungi is
based on their sexual spores.
Fungi that do not form sexual
spores are termed "imperfect" and
are classified as fungi imperfecti.

8.  Most fungi of medical interest propagate asexually by forming conidia
(asexual spores) from the sides or ends of specialized structures (Figure
47–1). The shape, color, and arrangement of conidia aid in the
identification of fungi. Some important conidia are
 (1) arthrospores, which arise by fragmentation of the ends of hyphae
 (2) chlamydospores, which are rounded, thick-walled, and quite
resistant.
 (3) blastospores, which are formed by the budding process by which
yeasts reproduce asexually (some yeasts, e.g., C. albicans, can form
multiple buds that do not detach, thus producing sausagelike chains
called pseudohyphae, which can be used for identification).
 (4) sporangiospores, which are formed within a sac (sporangium) on a
stalk by molds such as Rhizopus and Mucor.

10. Key Points:
 fungi that are human pathogens, it should
be remembered that fungi are used in the
production of important foods, e.g., bread,
cheese, wine, and beer. Fungi are also
responsible for the spoilage of certain
foods. Because molds can grow in a drier,
more acidic, and higher-osmotic-pressure
environment than bacteria, they tend to be
involved in the spoilage of fruits, grains,
vegetables, and jams.

11. Pathogenesis
 The response to infection with many fungi is the formation of granulomas.
Granulomas are produced in the major systemic fungal diseases, e.g.,
coccidioidomycosis, histoplasmosis, and blastomycosis, as well as several
others. The cell-mediated immune response is involved in granuloma
formation. Acute suppuration, characterized by the presence of neutrophils in
the exudate, also occurs in certain fungal diseases such as aspergillosis and
sporotrichosis. Fungi do not have endotoxin in their cell walls and do not
produce bacterial- type exotoxins.
 Activation of the cell-mediated immune system results in a delayed
hypersensitivity skin test response to certain fungal antigens injected
intradermally. A positive skin test indicates exposure to the fungal antigen. It
does not imply current infection, because the exposure may have occurred in
the past. A negative skin test makes the diagnosis unlikely unless the patient is
immunocompromised. Because most people carry Candida as part of the
normal flora, skin testing with Candida antigens can be used to determine
whether cell-mediated immunity is normal.

13.  Intact skin is an effective host defense against certain
fungi (e.g., Candida, dermatophytes), but if the skin is
damaged, organisms can become established. The normal
flora of the skin and mucous membranes suppress fungi.
When the normal flora is inhibited, e.g., by antibiotics,
overgrowth of fungi such as C. albicans can occur.
 In the respiratory tract, the important host defenses are the
mucous membranes of the nasopharynx, which trap
inhaled fungal spores, and alveolar macrophages.
Circulating IgG and IgM are produced in response to
fungal infection, but their role in protection from disease
is uncertain.

14. Fungal Toxins & Allergies
 Ingestion of Amanita mushrooms causes liver necrosis
due to the presence of two fungal toxins, amanitin and
phylloidin. Amanitin inhibits the RNA polymerase that
synthesizes cellular mRNA.
 Ingestion of peanuts and grains contaminated with
Aspergillus flavus causes liver cancer due to the
presence of aflatoxin. Aflatoxin epoxide induces a
mutation in the p53 gene that results in a loss of the p53
tumor suppressor protein.
 Inhalation of the spores of Aspergillus fumigatus can
cause allergic bronchopulmonary aspergillosis. This is
an IgE-mediated immediate hypersensitivity response.

16. Antifungal Therapy
 The drugs used to treat bacterial diseases have no effect on fungal diseases. For
example, penicillins and aminoglycosides inhibit the growth of many bacteria but
do not affect the growth of fungi. This difference is explained by the presence of
certain structures in bacteria, e.g., peptidoglycan and 70S ribosomes, that are
absent in fungi.
 The most effective antifungal drugs, amphotericin B and the various azoles,
exploit the presence of ergosterol in fungal cell membranes that is not found in
bacterial or human cell membranes. Amphotericin B disrupts fungal cell
membranes at the site of ergosterol and azole drugs inhibit the synthesis of
ergosterol, which is an essential component of fungal membranes. Another
antifungal drug, caspofungin , inhibits the synthesis of -glucan, which is found in
fungal cell walls but not in bacterial cell walls. Human cells do not have a cell
wall.
 There is no clinically significant resistance to antifungal drugs.