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Mycology
TEACHERS :
Mrs. IRISH S. UDTOHAN
Mr. HARLEY PARTOSA
Learning objectives

Describe Explain Discuss

Describe fungal Explain the Discuss the role of

classification, pathogenesis of Fungi in disease.
structure, and Fungal disease.
replication.
 Importance of Fungi
• The fungi represent a ubiquitous and diverse group of organisms, the main purpose of
which is to degrade organic matter.
• They are heterotrophic and acquire their nutrition in different forms:

saprobes (organisms symbionts (organisms commensals (organisms living
in a close relationship in which
that live on dead or that live together and in one benefits from the
decaying matter) which the association is relationship and the other
neither benefits nor is harmed)
of mutual advantage)
parasites (organisms that
live on or within a host
from which they derive
benefits without making
any useful contribution in
return
 Importance of Fungi
• Fungi have emerged in the past two decades as major causes of
human disease, especially among those individuals who are
immunocompromised or hospitalized with serious underlying
diseases. Among these patient groups, fungi serve as opportunistic
pathogens, causing considerable morbidity and mortality.
• The overall incidence of specific invasive mycoses continues to
increase with time, and the list of opportunistic fungal pathogens
likewise increases each year. This increase in fungal infections can
be attributed to the ever-growing number of immunocompromised
patients, including transplant patients, individuals with acquired
immunodeficiency syndrome (AIDS), patients with cancer and
undergoing chemotherapy, and those individuals who are hospitalized
with other serious underlying conditions and who undergo a variety
of invasive procedures.
Fungal Taxonomy, structure, and
Replication
• The fungi are classified in their own separate kingdom called Kingdom Fungi.
They are eukaryotic organisms that are distinguished from other eukaryotes by a
rigid cell wall composed of chitin and glucan and a cell membrane in which
ergosterol is substituted for cholesterol as the major sterol component .
• Classical fungal taxonomy relies heavily on morphology and mode of spore
production. Increasingly, however, ultra-structural features and biochemical and
molecular characteristics are brought to bear, often resulting in changes in the
original taxonomic designation.
• Fungi may be unicellular or multicellular. The simplest grouping, based on
morphology, lumps fungi into either yeast or molds.
Fungal Taxonomy,
structure, and A yeast can be defined morphologically as a cell that reproduces by budding or fission, in
which a progenitor or “mother” cell pinches off a portion of itself to produce a progeny or
“daughter” cell.
Replication

The daughter cells may elongate to form sausage-like pseudohyphae. Yeasts are usually
unicellular and produce round, pasty, or mucoid colonies on agar. Molds, on the other hand,
are multicellular organisms consisting of threadlike tubular structures, called hyphae, which
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). The hyphae
form together to produce a mat like structure called amycelium.
Fungal Taxonomy, • The colonies formed by molds are often described as filamentous, hairy, or woolly. When
structure, and growing on agar or other solid surfaces, molds produce hyphae, termed vegetative hyphae,
which grow on or beneath the surface of the culture medium, and hyphae that project above
Replication the surface of the medium (aerial hyphae).

• The aerial hyphae may produce specialized structures known as conidia (asexual
reproductive elements). The conidia may be produced by either a blastic (budding) process
or a thallic process, in which hyphal segments fragment into individual cells or
arthroconidia.

• 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 they may
exist in both a yeast form and a mold form. Most fungi exhibit aerobic respiration
Fungal Taxonomy, structure, &
Replication

Glomeromycota
 Classification of Human Mycoses
• In addition to the formal taxonomic classification of fungi, fungal infections may be classified
according to the tissues infected and by specific characteristics of organism groups. These
classifications include the superficial, cutaneous,

SUPERFICIAL CUTANEOUS MYCOSES SUBCUTANEOUS MYCOSES ENDEMIC MYCOSES

MYCOSES
Infections that are limited to
the very superficial surfaces
of the skin and hair. They
are nondestructive and of
cosmetic importance only.
E.g. pityriasis versicolor
& Tinea nigra.
Infections of the keratinized
layer of skin, hair, and nails.
These infections may elicit a
host response and become
symptomatic. Infections of the
skin involving these organisms
are called dermatophytes, e.g.
Tinea unguium.
Involve the deeper layers of the skin,
including the cornea, muscle, &
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 & remain localized, causing
abscess formation, nonhealing ulcers,
and draining sinus tracts, e.g.
Cladosporium spp.
Infections caused by classic
dimorphic fungal pathogens,
e.g. H. casulatum. These fungi
exhibit thermal dimorphism
and are generally confined to
geographic regions in which
they occupy specific ecological
niches. Also often referred to as
systemic mycoses
Classification of Human Mycoses
• In addition to the formal taxonomic classification of fungi, fungal infections may be classified
according to the tissues infected and by specific characteristics of organism groups. These
classifications include the superficial, cutaneous,

OPPORTUNISTIC MYCOSES
Infections attributable to fungi that are normally found as human commensals
or in the environment. The most common opportunistic fungal pathogens are
the yeasts Candida spp. and C. neoformans.
 PATHOGENESIS OF FUNGAL
DISEASE
• Although a great deal is known regarding the molecular and genetic basis for bacterial and viral pathogenesis,
our understanding of the pathogenesis of fungal infections is limited. Relatively few fungi are sufficiently
virulent to be considered primary pathogens .
• Primary pathogens are capable of initiating infection in a normal, apparently immunocompetent host. They are
able to colonize the host, find a suitable microenvironmental niche with sufficient nutritional substrates, avoid or
subvert the normal host defense mechanisms, and then multiply within the microenvironmental niche.
• When large numbers of conidia of any of these four fungi are inhaled by humans, even if these individuals are
healthy and immunocompetent, infection and colonization, tissue invasion, and systemic spread of the pathogen
commonly occur. As with most primary microbial pathogens, these fungi may also serve as opportunistic
pathogens, given that the more severe forms of each mycosis are seen most often in individuals who are
compromised in their innate and/or acquired immune defenses.
 PATHOGENESIS OF FUNGAL
DISEASE
PRIMARY FUNGAL PATHOGENS
• All of the primary systemic fungal pathogens are agents of respiratory infections, and none are
obligate parasites. Each has a saprobic phase characterized by filamentous septate hyphae, typically
found in soil or decaying vegetation, that produce the airborne infectious cells. Likewise, the
parasitic phase of each fungus is adapted to grow at 37° C and to reproduce asexually in the
alternative environmental niche of the host respiratory mucosa. This ability to exist in alternate
morphogenic forms (dimorphism) is one of several special characteristics (virulence factors)
that allow these fungi to cope with the hostile environmental conditions of the host.
PATHOGENESIS OF FUNGAL
DISEASE
 PATHOGENESIS OF FUNGAL
DISEASE
MODULATION OF YEAST AND HOST IMMUNE SYSTEM
• The main immunoreactive moiety present on the surface of the yeast cells, but not on the conidia of B. dermatitidis, is
a 120-kDa cell wall glycoprotein, BAD1 (formerly WI-1). This glycoprotein appears to play a key role in the
pathogenesis of B. dermatitidis, in that it promotes adhesion of the yeast cell to macrophages and elicits a potent
response of both the humoral and cellular immune systems. BAD1 is expressed by all virulent isolates of B.
dermatitidis examined thus far.
• In addition to its role in adhesion, BAD1 has been shown to modulate host immunity early in the course of infection,
facilitating the establishment of B. dermatitidis in the lung. BAD1 interferes with host immunity by blocking the
production of the proinflammatory cytokine, tumor necrosis factor (TNF)-α, by both macrophages and
neutrophils, through transforming growth factor (TGF)-β–dependent and (TGF)-β–independent mechanisms.
BAD1 displayed on the surface of B. dermatitidis yeast cells induces phagocyte TGF-β production, which suppresses
TNF-α production.
 PATHOGENESIS OF FUNGAL
DISEASE
MODULATION OF YEAST AND HOST IMMUNE SYSTEM
• It also appears that the carbohydrate composition of the yeast cell wall plays a role in the presentation
and shedding of BAD1 and thus in pathogenicity. One of the major components of the yeast cell wall is
1,3-α-glucan. There is an inverse relationship between the amount of 1,3-α-glucan present in the cell wall of B.
dermatitidis and the amount of detectable BAD1 at the cell surface.
• Virulent strains of B. dermatitidis produce yeast cells that have thickened walls containing large amounts of
1,3-α-glucan and, when mature, have little detectable BAD1 on their cell surface. Conversely, avirulent
strains exhibit thin walls that lack 1,3-α-glucan but have abundant BAD1 on their surface. It is speculated
that the incorporation of 1,3-α-glucan into the cell wall masks the BAD1 surface glycoprotein and plays a role in
releasing a modified antigen (85-kDa component) into the microenvironment of the infection site. By masking
the BAD1 antigen, the yeast is able to escape recognition by macrophages and disseminate hematogenously.
 PATHOGENESIS OF FUNGAL
DISEASE
PRESENTATION OF SURFACE ANTIGEN MODULATES
• Different subsets of CD4 T-helper (TH) cells exist that secrete different patterns of cytokines in response to an
antigenic stimulus. After an initial encounter with an antigen, TH cells may become polarized, secreting
predominantly interleukin (IL)-2 and interferon (IFN)-γ (TH1 pattern) or predominantly IL-4, IL-5, and IL-10
(TH2 pattern).
• IFN-γ and IL-2 activate macrophages and cytotoxic T and natural killer (NK) cells, respectively, for clearance of
intracellular organisms; whereas TH2 cytokines favor B-cell growth and differentiation, isotype switching to
immunoglobulin (Ig) E, and eosinophil differentiation and activation, which are responses that may lead to
protection against some pathogens, they also have been implicated in allergy and hypersensitivity reactions.
 PATHOGENESIS OF FUNGAL
DISEASE
UREASE PRODUCTION
• The environmental niche for the saprobic form of C. immitis is alkaline desert soil. Both saprobic and parasitic phases of this organism have
been shown to release ammonia and ammonium ions when grown in vitro, resulting in an alkalinization of the culture medium. The
endospores of C. immitis release much more ammonia/ammonium ions than do spherules, when grown in any acidic (pH 5.0) conditions.
Newly released endospores have been shown to be surrounded by an alkaline halo produced by the ammonia/ ammonium ions.
• The endospores of C. immitis are readily phagocytosed by alveolar macrophages but once ingested are able to survive
intracellularly. It has been shown that viable intracellular endospores are surrounded by an alkaline halo at their cell surface,
suggesting that the production of ammonia/ammonium ions may contribute to the survival of the pathogen within the phagosome of
the activated macrophage. The ability of C. immitis to generate an alkaline microenvironment and to respond to acidification by
increasing the amount of ammonia/ammonium ions released from its parasitic cells are features that may contribute to the pathogenesisof
this fungus. Although the details of ammonia generation and how cell-surface alkalinity affects phagocyte function are poorly understood, it
has been proposed that the major source of ammonia produced by C. immitis is caused by urease activity. Urease is a metalloenzyme
that is localized in the cytoplasmic fraction of microbial cells; itcatalyzes the hydrolysis of urea to yield ammonia and carbamate.
 PATHOGENESIS OF FUNGAL
DISEASE
EXTRACELLULAR PROTEINASES
• Fungal pathogens produce an array of acid, neutral, and alkaline proteinases that are active over a wide pH range and exhibit
broad substrate specificity. It has been suggested that certain extracellular enzymes secreted by fungi may play key roles in
invasive growth that may ultimately lead to the death of the infected host. Secreted proteinases may permit the ingress of skin
and mucosal barriers, partial neutralization of active host defenses, transmigration of endothelial layers, and subsequent
hematogenous dissemination, leading to the establishment of infection in various anatomic sites.
• C. immitis, as a primary fungal pathogen, is able to breach the respiratory mucosal barrier, enter the bloodstream and/ or the
lymphatic system, and disseminate to other organs of the body. Both the saprobic (conidial cell) and parasitic forms of the
fungus express several proteinases during cell growth. The conidial cell produces a 36-kDa extracellular proteinase capable
of breaking down human collagen, elastin, and hemoglobin, as well as IgG and IgA. Cleavage of secretory
immunoglobulins by opportunistic fungal pathogens has been correlated with the ability of these organisms to colonize
the host mucosa. A 66-kDa alkaline proteinase capable of digesting structural proteins, found in lung tissue, is thought to
be secreted during the entire course of disease caused by C. immitis.
 PATHOGENESIS OF FUNGAL
DISEASE
MOLECULAR MIMICRY
• When molecules produced by a pathogenic microbe are structurally, antigenically, and functionally
similar to host molecules, this characteristic is termed molecular mimicry. In some instances, infection may
result in the generation of antibodies by the host that cross-react with host tissues and produce an autoimmune-
type pathology. Fungi have been shown to produce molecules that are functionally, but not necessarily
structurally, similar to host molecules (“functional mimicry”).
 PATHOGENESIS OF FUNGAL
DISEASE
LIVING INSIDE MACROPHAGES HOST
• Conversion of inhaled conidia of H. capsulatum to yeast cells is critical for survival of the pathogen within the host and occurs
within hours of infection. Although theoretically a single conidium may be sufficient to establish an infection, it is usually
assumed that a very large conidial inoculum is necessary to establish disseminated disease in a healthy, immunocompetent
individual. The phagocytes that are mobilized to the site of infection are effective in killing ingested conidia but are less so
against the yeast form.
• The fact that the macrophages are the primary host cells in which the yeast phase of H. capsulatum resides is thought to be an
important strategy for survival and dissemination of the pathogen. H. capsulatum yeasts gain refuge from extracellular
obstacles such as antimicrobial lung surfactant proteins by engaging the β-integrin family of phagocytic receptors to
promote entry into macrophages. In addition, H. capsulatum yeasts conceal immunostimulatory β-glucans to avoid
triggering signaling receptors such as the β-glucan receptor Dectin-1.
• H. capsulatum yeasts counteract phagocyte-produced reactive oxygen species by expression of oxidative stress defense
enzymes including an extracellular superoxide dismutase and an extracellular catalase. There are several factors thought to
be important in the ability of the fungus to persist within the phagolysosome of the macrophage and add significantly to
the pathogenicity of the organism: pH modulation, iron and calcium uptake, and alteration of the yeast cell wall.
 PATHOGENESIS OF FUNGAL
DISEASE
ALTERATION OF YEAST CELL WALL COMPOSITION
• Similar to B. dermatitidis, most H. capsulatum strains have 1,3-α-glucan in their cell wall. Wild-type yeasts with 1,3-α-
glucan can infect and survive within macrophages and can proliferate within the phagolysosome and ultimately kill the
phagocyte, releasing yeast cells that go on to infect new macrophages. In contrast to the wild-type parent strain,
spontaneous mutants of H. capsulatum that have lost the 1,3-α-glucan component have been shown to have
significantly attenuated virulence and may infect and persist within macrophages without harm to the host cell.
Functionally, α-glucan promotes Histoplasma virulence by preventing recognition of yeast by host immune cells. The
α-glucan polysaccharide forms the outermost surface of the yeast cell wall, effectively concealing cell wall β-glucans
that would normally be detected by Dectin-1 receptors on host macrophages. Dectin-1 is the primary receptor for the
detection of fungal β-glucans, inducing an inflammatory response that may include increased production of reactive
oxygen species and release of proinflammatory cytokines. Notably, certain North American strains of H. capsulatum
naturally lack α-glucan; they show variable recognition by Dectin-1 yet remain virulent. The molecular mechanism by
which these strains have circumvented the need for α-glucan remains unknown. Thus it appears that distinctive
microenvironments found within host cells can influence the selection of variants that have the potential for long-term
persistence within the host, as well as those that produce a more rapidly proliferative process.
 PATHOGENESIS OF FUNGAL
DISEASE
OPPORTUNISTIC PATHOGENS
• The state of the host is of primary importance in determining the pathogenicity of opportunistic
fungal pathogens, such as Candida spp., C. neoformans, and Aspergillus spp. In most instances,
these organisms may exist as benign colonizers or as environmental saprobes and only cause serious
infection when there is a breakdown of host defenses. There are factors associated with these
organisms, however, that may be considered “virulence factors,” in that they contribute to the disease
process and in some instances may explain the differences in pathogenicity of the various organisms.
ROLE OF FUNGI IN DISEASE
• Mycotic diseases in humans develop as pathogenic processes in one or more organ systems. The affected systems
may be as superficial as the outer layers of the skin or as deep as the heart, central nervous system, or abdominal
viscera. Although a single fungus may be associated with infection involving a single organ system (e.g.,
Cryptococcus neoformans and the central nervous system), more often several different organisms may produce a
similar disease syndrome. Because the management of a given infection may differ according to the etiologic
agent, to guide subsequent diagnostic and therapeutic efforts it is useful to develop a differential diagnosis that
includes the most likely fungal pathogens.

• Because the development of a fungal infection depends on factors that often outweigh the virulence potential of the
infecting organism, one must take into account numerous factors, such as the immune status of the host, the
opportunity for interaction between host and fungus (e.g., Is the fungus endogenous to the patient or exogenous?),
and the potential infectious dose (e.g., in the case of an endemic dimorphic fungus) in determining the possibility
of a fungal infection, the significance of the microbiologic data (e.g., culture results), and the necessity to treat and
with what agent. Fungal infections often occur in very sick patients, and it is not possible to summarize here the
incredibly complex interactions that ultimately lead to the establishment of infection and disease in each organ
system.
ROLE OF
FUNGI IN
DISEASE