Introduction to Medical Mycology

1
 Outline

• Introduction
• Characteristics of fungi
• Morphology of fungi
• Classification of medical important fungi
• Reproduction and metabolism of fungi
• Pathogenesis of fungal diseases

2
 1. Introduction

❖ Mycology is study of fungi.

➢ Genetic properties
➢Biochemical properties
➢Their taxonomy and
➢Their use to humans

3
 Medical Mycology

• Medical Mycology is the study of fungi that infect human.

4
 Medical Mycology…
▪A fungus is any member of the group of eukaryotic organisms that are classified
as a kingdom Fungi.

5
1.1 General characteristics of fungi

• Eukaryotic (e.g., true nucleus, 80S

ribosomes, Mt, ER)

• Complex carbohydrate cell walls:

• Chitin and glucan: give

rigidity to cell wall
• Mannan: linked to surface
proteins
• Ergosterol is major membrane

sterol

6
 Characteristics …

➢Non-photosynthetic-lack chlorophyll
➢Heterotrophs
➢Saprophytic-Decomposers
➢Symbionts- mutualistic
➢Parasites

➢Reproduces by asexually, sexually or both

➢ Unicellular or multicellular
➢Natural habitat
➢Found Everywhere
7
 Characteristics…

• Non motility:

• Most fungi are obligate aerobes

• Some are facultative anaerobes
• Grow best at acidic pH <5 (wide pH range)

• Macroscopic and/or Microscopic fungi

 Grow as
 Yeasts
 Molds
 Dimorphism
Hyphae 8
 Characteristics…
• All fungi are gram (+)
• Difference between fungi & bacteria
Features Fungi Bacteria
• Nucleus eukaryotic prokaryotic
• Mitochondria present absent
• Endoplasmic R. present absent
• Cell membrane sterols cholesterol
• Cell wall chitin peptidoglycan
• Spores For reproduction for survival
• Replication Binary fission/budding Binary fission
• Ribosomes 80 S 70 S

9
 1.2 Morphology of the Fungi

• Fungi : Are generally larger than bacteria

• Individual cell size: ranging from 1 to 30 µm diameter.

Fungal
morphology

Yeasts Molds Dimorphic

10
 Mold
❖Mold
✓Molds are multicellular filamentous fungi.
✓The body is called thallus.
✓The thallus is made of hyphae.
❖Hyphae: are cylindrical, tube like structure.
✓Basic microscopic unit of the molds
✓Responsible for the fluffy appearance of the macroscopic mold
colony.
✓Multi-cellular
✓Branching Filaments
• Mycelium: grow as an intertwined mass of filamentous hyphae.

11
Mold

12
 Molds …
• Fungal hyphae could be

• Septated hyphae:
• filaments with cross-walls or
• septa that partition the hyphae in to individual cellular
compartments.
• have spores that allow the migration of cytoplasm and many
organelles.

• Aseptate hyphae ( non-septate or coenocytes) - no physical

boundaries to distinguish individual cells in the hyphae.

13
 Septated and aseptated hyphae

(a) septate hyphae (b) aseptate hyphae

14
Mold form
Arial hyphae
• Fungal filaments or
• Hyphae that protrude above the
surface
• Produce asexual spore

Vegetative hyphae
• Nutrient absorbing and water
exchanging portion of the fungi.
• Grows in or on a substrate.
• Are actively growing and form the
main body of the colony.
15
 1.2.2 Yeasts

• Monomorphic: existing as single cell.

• It is distinguished by
• Shape (round to oval)
• are usually large (5 to 8 µm in
diameter).
• Mode of asexual reproduction
• Fission formation
• Blastoconidia formation (budding)

16
 1.2.3 Dimorphism
• Existing as yeast or mold
• Most human pathogenic fungi are
dimorphic.
• Forming hyphae at ambient °𝑇 but
yeasts at body °𝑇.
• Dimorphism is regulated by factors
such as
• Temperature
• At 37C: Yeast form (in vivo).
• At 25C: Mold form.
• pH
• CO2 concentration
• Level of nutrition etc.

17
1.2.4 Reproduction

➢ Sporulation (process of making spores) is the principal

means by which fungi reproduce and spread through the
environment.

➢ Fungal spores are metabolically dormant, protected cells.

➢ They can be borne by air or water to new sites, where they

germinate and establish colonies.

➢ Mold reproduce by Asexual spores and Yeast reproduce with

budding and sexual spore

18
Fungal repro cont’d…
➢ Spores can be generated either asexually or sexually

➢ Many fungi can produce both sexual and asexual spores.

➢ Fungi that exhibit sexual phase are known as the perfect fungi

➢ Fungi imperfecti or deuteromycetes are the designation for a

type of fungi in which the sexual cycle are either unknown or

missing entirely.

➢ Sexual spores are rarely agents of human disease.

19
 1.3 TAXONOMY
Kingdom Characteristic Example
Monera Prokaryocyte • Bacteria
• Archaea
Protista Eukaryocyte • Algae
• Protozoa
Fungi Eukaryocyte * • Fungi
Plants Eukaryocyte • Plants
• Moss
Animals Eukaryocyte * • Arthropods
• Mammals
• MAN

*This common characteristic between animals and fungi is responsible

for the therapeutic dilemma in anti-mycotic therapy.

20
 1.3.1 Classifications of medical important Fungi

• Medically important
fungi are:
• Classified into five
phyla based on
• Spore types
• Morphology of hyphae
• Sexual cycles
• Phylogenic relationship

21
 Classifications…
5 Phyla in the division of fungi

Ascomycota Basidiomycota Zygomycota Chytridiomycota Deutromycota

22
Characteristics of clinically important fungi
Typical
GENUS Septation Phylum
Growth
Superficial fungi
Malassezia furfur Yeast - Basidiomycota
Hortae werneckii Mold + Ascomycota
Piedraia hortae Mold + Ascomycota
Trichosporon Mold + Ascomycota
cutaneum
Trichosporon Mold + Ascomycota
beigelii
Cutaneous fungi
Epidermophyton Mold + Ascomycota
Microsporum Mold + Ascomycota
Trichophyton Mold + Ascomycota
23
Characteristics of clinically important fungi
GENUS Typical Growth Septation Phylum
Subcutaneous Fungi
Sporothrix Dimorphic + Ascomycota
Opportunistic Fungi
Aspergillus Mold + Ascomycota
Candida Yeast + Ascomycota
Mucor Mold – Zygomycota
Pneumocystis Cysts Ascomycota
Rhizopus Mold – Zygomycota
Systemic Fungi
Blastomyces Dimorphic + Ascomycota
Coccidioides Dimorphic + Ascomycota
Cryptococcus Yeast Basidiomycota
Histoplasma Dimorphic + Ascomycota
24
 1.4 Metabolism in the Fungi

Fungal nutrition

Symbiont
Saprophytic Parasitic
(mutualism)

• Free living organisms ▪ Both partners benefit. • Live on or within a host.

• Obtain nutrients from ▪ Lichens (association of • The relationship is harmful

dead organic matter fungi + algae) to the host

• Important decomposers in ▪ Mycorrhiza (fungi +plant • Acquire nutrients by

biochemical cycles roots attacking animals or plants.

25
 Pathogenesis of fungal Infection

• Less is known about their

➢Pathogenic mechanisms and
➢Virulence factors involved in fungal infections

• Most fungi are opportunists

• Producing serious disease only in individuals with impaired host

defense systems.

• Fungi have developed some mechanisms to colonize human

hosts.

26
 Pathogenesis…

• The ability to grow at 37°C

• Capsule- Cryptococcus neoformans

• Pseudohyphae- C. albicans

• Dimorphism

• Secondary metabolites –toxins

• Biofilm

• Production of extracellular enzymes

• Keratinase- dermatophytes.
27
 Pathogenesis and Predisposing Factors

Host Defenses

▪ The immunologic status of the host

▪ Humoral and cell mediated immunity

Increased moisture
• It creates a more hospitable environment for

proliferation of pathogens.

28
 Predisposing Factors
• Obesity
• Promotes accumulation of surface moisture in body
folds.

• Exposes the underlying tissue to environment

• e.g. Wound, Burn, Invasive medication procedures
• It disrupts the physical integrity of the skin.
• It facilitate development of skin infection.

29
 Predisposing Factors…
❑Tight clothing: creates moisture
• It also disrupts the physical integrity of skin through
continual abrasion.
❑Underlying debilitating disease
➢Diabetics
➢HIV infection
➢Cancer
❑Immune suppressive chemotherapy
❑Corticosteroids
❑Cancer therapy
❑Malnutrition
• It impairs immunologic system.
30
 1.5 Overview of Fungal Disease

Fungal Disease

1.5.1. Fungal Allergies 1.5.2 Mycotoxicosis 1.5.3 Fungal Infection

• Spore in the air • Caused by fungal toxin

• By products
• Sick building
• May result from:
syndrome • Ingestion of fungi-poisonous mushroom
• Molds • Contaminated foods.
• E.g. Phalloidin, egotism, Amanitin,
• Common in with
Aflatoxin
other allergens • Produced when the fungus grows in moist
environment at relatively high °T.
31
 1.5.3 Fungal Infection
• Fungi cause the most persistent and disfiguring disease still prevalent
through out the world.

• Diseases caused by fungi are collectively called mycoses (singular,

mycosis).

• The incidence of the disease is related to the degree of exposure to

fungi in living conditions, occupation, and leisure activities and to
immune status.

• There are four general categories on the basis of the primary tissue
affinity of the pathogen.

32
 Mycoses…
• Superficial and cutaneous mycoses:
—Skin, hair & nails
—Mild but chronic disease
 Deep mycoses:
 Subcutaneous
 Mucocutaneous
 Systemic mycoses
—2 types: primary and opportunistic
— Caused by soil saprophytes
— Infection is accidental
— Range from asymptomatic infection to fatal disease.

33
1. Superficial Mycoses
• Are confined to the outer most dead
layers of skin and its appendages (hair
and nails).
• No contact with living tissue hence, no
inflammatory response
• symptoms- discoloration, scaling, or
de-pigmentation of the skin.
• Do not elicit a cellular response from
the host.
• Infections are generally painless.
34
1. Superficial Mycoses …

Diseases Organism Tissue

Tinea versicolor Malassezia furfur Skin

Tinea nigra Exophiala werneckii Skin

White piedra Piedraia hortae Hair

Black piedra Trichosporon beigelii Hair

35
 Characteristics of superficial fungi
FUNGAL GROWTH
In Culture
Fungus In Lesion Infection Site Disease
(25°c)
Superficial fungi

Malassezia Skin (pink to Pityriasis (tinea)

Yeast Yeast
furfur brown) versicolor

Exophiala Septate hyphae, Skin (brown to

Yeast (mold) Tinea nigra
werneckii ellipsoidal cells black)
Trichosporon
Septate hyphae Mold Hair (white) White piedra
cutaneum
Mold,
Piedraia hortae Septate hyphae Hair (black) Black piedra
ascospores

36
 2. Cutaneous Mycoses

Fungal infections strictly confined to

➢The keratinized layer of skin, hair, and nails.
➢Involve the deeper layers of the epidermis and its integuments,
the hair and nails.
➢Caused by homogeneous group of closely related fungi known
as dermatophytes.
➢The diseases they cause dermatophytosis
➢ Ringworm (Tinea): Common terms used to refer these diseases.
➢Because they tend to develop in circular, scaly patches.
37
 Cutaneous Mycoses…

➢Contact with living tissue.

➢Elicit an inflammatory and allergic response.
➢Resulting in more serious skin diseases with
uncomfortable painful and
➢sometimes even crippling symptoms

38
 Cutaneous Mycoses…
• Symptoms - include
• Itching, Scaling or ring like
patches of the skin;
• Brittle or broken hairs;
• Thick discolored nails.

39
Clinical finding

40
Agents of Subcutaneous Mycoses
FUNGAL GROWTH
IN
Fungus In Lesion Culture Infection Site Disease
(25°c)
Dermatophytes
Microsporum
Septate hyphae Mold Hair, skin Ringworm
canis
M. audouini Septate hyphae Mold Hair Ringworm
M.gypseum Septate hyphae Mold Hair, skin Ringworm
Trichophyton
Septate hyphae Mold Hair, skin, nails Ringworm
tonsurans
T.rubrum Septate hyphae Mold Hair, skin, nails Ringworm

T.mentagrophytes Septate hyphae Mold Hair, skin Ringworm

T.violaceum Septate hyphae Mold Hair, skin, nails Ringworm

E. floccosum Septate hyphae Mold Skin Ringworm

41
 Dermatophyte species
• 3 Genera
• Trichophyton-causes infection of hair, skin, and nail.
• Microsporum-causes infection of hair and skin.
• Epidermophyton-causes infection of skin and nails.

Microscopic appearance of various

dermatophyte species (LPCB mount)

A. Trichophyton mentagrophytes;
B. Microsporum canis and
C. Epidermophyton floccosum

42
 3. Subcutaneous Mycoses

• Are infections confined to :

• The subcutaneous tissue (dermis or fatty tissues).

• The deeper layer of the skin.

• Normally reside in soil or on vegetation.

• They penetrate the skin to the subcutaneous tissue by

➢traumatic inoculation with contaminated material.

43
 Subcutaneous Mycosis…

• Symptoms include :

• Ulcers, that progress and do not heal.

• The presence of draining sinus tracts.

• Granulomatous lesion

• Mycoses in this category are :

➢Sporotrichosis-Sporothrix schenckii

➢Rhinosporidiosis-R.seeberi

44
 Subcutaneous Mycosis…

• Chromoblastomycosis: • Phaeohyphomycosis:
• Fonsecaea spp. • Alternaria
• Phialophora spp. • Bipolaris
• Cladosporium spp. • Cladosporium
• Cladophialophora • Curvularia
• Phialophora
• Exophiala
• Fonsecaea
• Hyalohyphomycosis • Phoma
• Acremonium spp. • Ulocladium
• Fusarium spp. • Xylohypha
• Paecilomyces spp.
• Scedosporium spp.
45
 Subcutaneous Mycosis…
• Mycetoma: 2 types
• Actinomycotic-bacteria
• Eumycotic-fungi
• Pseudallescheria boydii
• Madurella mycetomatis
• Madurella grisea
• Exophiala jeanselmei
• Acremonium falciforme
• Lesions lead to swollen extremities
• Draining sinuses
• Sulfur granules

46
 Agents of Subcutaneous Mycoses

Fungal Growth
In Culture
Fungus In Lesion Infection Site Disease
(25°C)
Subcutaneous fungi
Sporothrix Subcutaneous, Sporotrichos
Cigar-shaped yeast Mold
schenckii lymphatic spread is
Fonsecaea Chromoblast
Muriform body Mold Wart-like foot lesions
pedrosoi omycosis
Phialophora Chromoblast
Muriform body Mold Wart-like foot lesions
verrucosa omycosis
Cladophialophor
a Chromoblast
Muriform body Mold Wart-like foot lesions
(Cladosporium) omycosis
carrionii

47
 Mucocutaneous
• Oral thrush

• Esophageal candidiasis

• Vulvovaginal candidiasis (VVC)

• The second Most Common Cause of vaginal symptoms after

Bacterial vaginosis.

• Like Bacterial vaginosis, it occur after a disruption of the normal

microbiota.

48
 4. Systemic (Deep) Mycoses

• Are caused by true pathogenic and/or opportunistic fungi

• Affect internal organs or tissues of the body.

• The organisms responsible for systemic mycoses could be:

1. True pathogens: Infect normal healthy individuals
2. Opportunistic pathogens:
• Primarily infect debilitated, and/or IC individuals

49
Deep mycosis

• True pathogens
• Coccidioidomycosis • Dimorphic fungi
• Histoplasmosis • Acquired via RT
• Primary organ is lung
• Blastomycosis and
• Paracoccidioidomycosis
• Opportunistic or OFIs
• Candidiasis
• Aspergillosis
• Cryptococcosis
• Pneumocystis pneumonia etc.

50
Systemic Mycosis…

• Symptoms
• very general as fever,
and fatigue;
• a chronic cough and
chest pain.

51
 Features of Systemic Fungal Pathogens
GROWTH

Culture Culture Primary Disseminated

Organism Tissue Source
at25°c at37°c Disease Disease

Cryptococcu
s Encapsulated Encapsulated Encapsulated Environment, Chronic
Pneumonia
neoformans, yeast yeast yeast worldwide meningitis
C. gattii

Mold, Small Pneumonia,

Histoplasma Environment, RES
tuberculate Small yeast intracellular hilar
capsulatum US Midwest enlargement
macroconidia yeast adenopathy

Skin and bone

Blastomyces Yeast Yeast Environment,
Mold Pneumonia lesions
dermatitidis US Midwest

Coccidioide
Pneumonia,
s Mold, Environment,
Spherules Spherules Valley fever meningitis,
immitis, C arthroconidia Sonoran desert
skin, and bone
posadasii
Mucocutaneou
Paracoccidi
Yeast, multiple Environment, s,
oides Mold Pneumonia
blastoconidia Latin America RES
brasiliensis

52
 Growth endemic dimorphic fungi

A. Histoplasma capsulatum.

B. Blastomyces dermatitidis

C. Paracoccidioides
brasiliensis

D. Coccidioides immitis

E. Talaromyces marneffei

Saprobic and parasitic phases of endemic dimorphic fungi.

53
 Agents of Opportunistic Mycoses
• OFIs are caused by a group of fungi which cause infections in patients who
are immunocompromised.

Growth
Culture Culture
Organism Tissue Source Infection
at 25°c at 37°c
Skin, mucous
membranes,
Candida Yeast Yeast Yeast Endogenous
urinary,
disseminated
Aspergillus Septated Mold Mold Environment Lung, disseminated

Rhinocerebral, lung,
Zygomycetes Non-septated Mold Mold Environment
disseminated
Elliptical
Pneumocystis None None Unknown Pneumonia (PCP)
spores

Zygomycetes: Most common genera are Absidia, Mucor, and Rhizopus

54