Mycology · Unit 28 of 28

Medical Mycology

TMU Medical Mycology deck, 52 slides The deck's summary slide sets 5 definitions and 8 questions — all answered in §7 Mycology is one of the five named review-question topics for this course

What is a fungus? ★★★

Fungi

Eukaryotic organisms — each fungal cell has at least one nucleus enclosed by a nuclear membrane, endoplasmic reticulum, mitochondria and a secretory apparatus. They do NOT contain chlorophyll. They are eukaryotic, SPORE-BEARING, NON-PHOTOSYNTHETIC microbes that exist widely in nature.

⭐ The relationship between fungi and humans

Beneficial	Harmful
Biodegradation and recycling of organic matter	About 400 species cause human disease — as opportunistic pathogens and pathogens
Source of food	MYCOSES — infections caused by fungi: superficial, cutaneous, subcutaneous, systemic or allergic disease
Seasoning and flavouring	Fungal toxins → poisoning
Antibiotics — penicillin is extracted from Penicillium	Cancer

Test yourself

Define fungi. → Eukaryotic, spore-bearing, non-photosynthetic microbes; each cell has at least one nucleus with a nuclear membrane, ER, mitochondria and secretory apparatus, and no chlorophyll
Give four benefits of fungi to humans. → Biodegradation and recycling of organic matter, food, seasoning and flavouring, antibiotics (penicillin from Penicillium)
Give four harms. → About 400 species cause human disease; mycoses (superficial, cutaneous, subcutaneous, systemic, allergic); fungal toxins causing poisoning; and cancer
Define a mycosis. → An infection caused by fungi

Structure of a fungal cell ★★★

Organism	Size
Viruses	0.08 µm
Cocci	0.8 µm
Bacilli	4–6 µm
Spirochaetes	8–10 µm
Fungi	10–15 µm — the largest

Component	Content
Cell wall	Multilayered and rigid: CHITIN, proteins, polysaccharides and lipids. NO peptidoglycan
Cell membrane	ERGOSTEROL instead of cholesterol — the target of some antifungal antibiotics, e.g. the azole derivatives: ketoconazole, fluconazole, itraconazole
Cytoplasm and organelles	Ribosome 80S · endoplasmic reticulum · mitochondria · Golgi body
Nucleus	One or more, with a nuclear membrane and nuclear pores
Capsule	e.g. Cryptococcus neoformans — thick and polysaccharide; a VIRULENCE FACTOR

Two molecules explain every antifungal drug — and every antibacterial failure

Fungi are eukaryotes, like us. That is the whole therapeutic problem: almost everything a fungal cell does, our cells do too, so there is very little to attack selectively.

The deck names the two differences that matter.

Chitin in the wall. Not peptidoglycan — so penicillin, which attacks peptidoglycan cross-linking (Unit 2 §3), does nothing. That is why the resistance list in §5 includes tetracycline, penicillin and streptomycin as agents fungi are resistant to. Human cells have no wall at all, so the fungal wall is a good target in principle.

Ergosterol instead of cholesterol in the membrane. This is the single most exploited difference in antifungal therapy. Azoles — ketoconazole, fluconazole, itraconazole — block ergosterol synthesis; amphotericin B and nystatin bind ergosterol directly and punch holes in the membrane.

And it explains the side effects: our membranes contain cholesterol, which is similar enough that amphotericin B binds it too — hence its notorious toxicity.

One letter of difference in a sterol; an entire drug class.

Test yourself

How big are fungi compared with bacteria? → 10–15 µm, larger than cocci (0.8 µm), bacilli (4–6 µm) and spirochaetes (8–10 µm)
What is the fungal cell wall made of? → Chitin, proteins, polysaccharides and lipids — multilayered and rigid, with NO peptidoglycan
What sterol is in the membrane, and why does it matter? → Ergosterol instead of cholesterol — the target of azoles (ketoconazole, fluconazole, itraconazole)
Which ribosome do fungi have? → 80S — a eukaryotic ribosome
Which fungus has a capsule, and what is it? → Cryptococcus neoformans — thick, polysaccharide, and a virulence factor

⭐ The two basic morphological forms ★★★

	Yeast form	Mould form
Cellularity	Unicellular	Multicellular
Shape	Roughly spherical	Hyphae and spores
Reproduction	BUDDING or fission; may form pseudohyphae / pseudomycelium	By spores
Colony	Moist or mucoid	Filamentous
Examples	**Cryptococcus neoformans · Candida albicans**	Penicillium and other moulds

Hyphae

Branching, threadlike filaments of fungi that elongate at their tips.

Classification of hyphae	Types
Based on structure	SEPTATE hyphae · COENOCYTIC (non-septate) hyphae
Based on function	VEGETATIVE hypha · AERIAL hypha · REPRODUCTIVE hypha — an aerial hypha that produces spores

Mycelium

A mass of hyphae collectively making up the mycelium.

Test yourself

Name the two basic morphological forms. → Yeast (unicellular, spherical, reproducing by budding or fission, moist mucoid colonies) and mould (multicellular, with hyphae and spores)
Define a hypha. → A branching, threadlike filament of fungus that elongates at its tip
How are hyphae classified? → By structure into septate and coenocytic (non-septate); by function into vegetative, aerial and reproductive (an aerial hypha producing spores)
Define a mycelium. → A mass of hyphae collectively
Give two yeast-form examples. → Cryptococcus neoformans and Candida albicans

⭐ Spores and dimorphism ★★★

Fungal spore

The reproductive structure or unit of fungi.

Sexual spores — by MEIOSIS, haploid	Asexual spores — by MITOSIS
Zygospores	Conidium — MACROconidia (large, multicelled) and MICROconidia (small, single-celled)
Ascospores	Thallospore
Basidiospores	Blastospore
Oospores	Chlamydospore · Arthrospore · Sporangiospore

⭐ Fungal spores versus bacterial spores — a set question

	Spores of FUNGI	Spores of BACTERIA
Resistance to heat	WEAK — killed at 60 °C in 1 hour	STRONG — survive 100 °C for 1–2 hours
Number	One hypha can produce MANY spores	One bacterial cell can form only ONE spore
Purpose	A REPRODUCTIVE form of fungi	NOT a reproductive form for bacteria — it is a survival form

Fungal dimorphism

Medically important fungi are DIMORPHIC — they grow as a YEAST form (the parasitic, tissue, unicellular form; e.g. Candida cultured at 35–37 °C) or as a MOULD form (the saprophytic, multicellular form; e.g. Candida cultured at 25 °C). The dimorphic transition depends on oxidation-reduction potential, pH and other factors, and RELATES TO PATHOGENICITY.

Dimorphic fungi: Coccidioides immitis · Paracoccidioides brasiliensis · Blastomyces dermatitidis · Histoplasma capsulatum.

Temperature is the switch, and 37 °C is the body

Yeast at 35–37 °C; mould at 25 °C. Those two numbers are body temperature and room temperature, and that is the entire point.

In the soil, at ambient temperature, the fungus grows as a mould — filamentous, producing airborne spores. Inhale those spores and, at 37 °C, the organism converts to the yeast form: single cells, no hyphae, small enough to live inside a macrophage.

That is why the deck says the transition relates to pathogenicity, and why §6 says the systemic mycoses overcome host physiological and cellular defences by changing their morphological form and often initiate in the lungs by inhalation of conidia.

Two practical consequences: the laboratory grows the diagnostic mould form at 25 °C while the patient's tissue shows the yeast form — so the same organism looks like two different things depending on where you look. And handling those cultures is hazardous, because a plate of mould is a plate of infectious spores.

Note also the contrast in the spore table: fungal spores are for reproduction and die at 60 °C; bacterial spores are for survival and resist 100 °C. Same word, opposite biology — which is exactly why Unit 7 said the criterion of sterilisation is killing bacterial spores.

Test yourself

Define a fungal spore. → The reproductive structure or unit of fungi
Name the sexual and asexual spores. → Sexual (meiosis): zygospores, ascospores, basidiospores, oospores. Asexual (mitosis): conidia (macro- and microconidia), thallospores, blastospores, chlamydospores, arthrospores, sporangiospores
Give three differences between fungal and bacterial spores. → Heat resistance weak (60 °C/1 h) vs strong (100 °C/1–2 h) · one hypha makes many vs one cell makes one · reproductive vs not reproductive
Define fungal dimorphism. → Growth as a yeast (parasitic, tissue, unicellular) form at 35–37 °C or a mould (saprophytic, multicellular) form at 25 °C, depending on redox potential and pH — and related to pathogenicity
Name four dimorphic fungi. → Coccidioides immitis, Paracoccidioides brasiliensis, Blastomyces dermatitidis, Histoplasma capsulatum

Cultivation and resistance ★★★

	Detail
Medium	SABOURAUD'S AGAR — 4% glucose, 1% peptone, pH 5.6
Conditions	22–28 °C, pH 4–6; high moisture and oxygen

Colony type	Description	Example
a · Yeast colony	Round, mucoid, creamy, opaque	*Cryptococcus neoformans*
b · Yeast-like colony	As above, but with pseudohyphae	*Candida albicans*
c · Filamentous colony	Hairy, fluffy and cottony	Mould — e.g. Penicillium

Resistant to	Sensitive to
Drying, UV, acid and alkali	Heat — killed at 60 °C for 1 hour
Tetracycline, penicillin, streptomycin and other ANTIBACTERIALS	Phenol (1–3%), iodine (2.5%), formalin (10%)
	Amphotericin B, ketoconazole, fluconazole, itraconazole, griseofulvin, nystatin

Test yourself

What medium, and what conditions? → Sabouraud's agar (4% glucose, 1% peptone, pH 5.6) at 22–28 °C, pH 4–6, with high moisture and oxygen
Name the three colony types with examples. → Yeast (round, mucoid, creamy, opaque — Cryptococcus) · yeast-like (Candida albicans) · filamentous, hairy, fluffy and cottony (moulds)
What are fungi resistant to? → Drying, UV, acid and alkali, and antibacterials such as tetracycline, penicillin and streptomycin
What are they sensitive to? → Heat (60 °C for 1 hour), phenol 1–3%, iodine 2.5%, formalin 10%, and the antifungals amphotericin B, the azoles, griseofulvin and nystatin

⭐ Pathogenicity and the five types of mycosis ★★★

About 400 fungal species cause human disease; 50–100 species are common. The major physiologic barriers against them are temperature, redox potential and cellular immune defences.

Human factors	Fungal factors
Low immunity state	Invasive structures, enzymes, toxins
Environmental exposure	Dimorphism · ability to block host cell-mediated immune defences

The deck's conclusion is worth quoting: “Generally, human mycosis development is related primarily to the HOST IMMUNE STATUS and ENVIRONMENTAL EXPOSURE, rather than to the infecting organism.”

Virulence factor	Example
Capsules — antiphagocytosis	**Cryptococcus neoformans, Histoplasma capsulatum**
Enzymes — digest host cells	Keratinase (dermatophytes)
Mycotoxins	Poisoning; mutagenic and carcinogenic

⭐ The five types of mycosis

Type	Detail
A · Pathogenic fungal infection	Four levels — below
B · Opportunistic fungal infection	Endogenous infection — e.g. thrush
C · Hypersensitivity	Allergens: hypha, spores, fungal products. Diseases: urticaria, rhinitis, asthma, allergic dermatitis
D · Mycotoxicosis	Mycotoxins ingested by humans → poisoning
E · Fungal toxins causing tumours	Aspergillus flavus → AFLATOXIN → HEPATOMA

A · Pathogenic fungal infection — by the tissue infected

Level	Detail
I · Superficial infection	Involves only the outermost layer of skin and hair shaft — the stratum corneum and hair cuticle. NO living tissue is invaded, NO pathological changes, NO cellular response; patients are often unaware. Pityriasis versicolor (Malassezia furfur, a lipophilic yeast) · tinea nigra (Exophiala werneckii)
II · Cutaneous infection	Deeper in the epidermis and keratinised tissues — skin, hair, nails. NO living tissue is invaded, but a variety of pathological changes (skin lesions) occur, from irritation by fungal growth and toxic metabolic products. DERMATOPHYTOSIS — TINEA (ringworm): tinea corporis, capitis, cruris, pedis (“athlete's foot”), unguium, barbae
III · Subcutaneous infection	Causative fungi are SOIL SAPROPHYTES; they involve the dermis, subcutaneous tissue and muscle, INVADE THROUGH TRAUMA, and cause CHRONIC GRANULOMATOUS disease. Chromoblastomycosis, sporotrichosis, mycetoma, lobomycosis, subcutaneous zygomycosis
IV · Dimorphic systemic mycoses	Dimorphic fungal pathogens OVERCOME host physiological and cellular defences BY CHANGING THEIR MORPHOLOGICAL FORM. Specifically organophilic; GEOGRAPHICALLY RESTRICTED; often initiate in the lungs by INHALATION OF CONIDIA; involve deep viscera. Blastomycosis — south-eastern and south-central North America · Coccidioidomycosis — south-western USA, Mexico, Central and parts of South America · Paracoccidioidomycosis — South and Central America · Histoplasmosis — endemic in certain areas of the USA

B · The opportunistic fungi

Disease	Organism	Detail
Candidiasis	*Candida albicans*	Exists in the human mouth, gut, vagina and skin surface. Mucocutaneous infection — thrush, vaginitis · organ infection — bronchitis, pneumonia, oesophagitis, enteritis, endocarditis, septicaemia · CNS infection — meningitis · allergic disease
Cryptococcosis	*Cryptococcus neoformans*	Round, CAPSULATE, 3–5 µm; grows on blood agar and Sabouraud's agar as a yeast-form colony. Saprophytic, widely present in SOIL and PIGEON FAECES; an opportunistic EXOGENOUS infection. Main portal of entry: the LUNG. Most cases asymptomatic; a few develop pneumonia; and CRYPTOCOCCAL MENINGITIS
Aspergillosis	*Aspergillus*	Pulmonary aspergillosis · mycotoxicosis and cancer
Mucormycosis	*Mucor*
PCP	*Pneumocystis carinii*	Pneumocystis carinii pneumonia — a MAJOR CAUSE OF DEATH among AIDS patients

“Related primarily to the host immune status, rather than to the infecting organism”

That sentence from the deck is the most important line in the unit, and it separates mycology from every module before it.

With Staphylococcus aureus or Vibrio cholerae, the organism brings toxins and invasins and can make a healthy person ill. Most fungi cannot. They are everywhere — in soil, in the air, on our skin, in our gut — and they are held off by intact skin, by body temperature, and above all by cell-mediated immunity.

So the fungal diseases that matter clinically are, overwhelmingly, diseases of the immunocompromised:

• Thrush and oesophageal candidiasis — after antibiotics (Unit 5 §3's loss of antagonism) or in AIDS
• Cryptococcal meningitis — the classic AIDS opportunist, from soil and pigeon droppings
• PCP — a major cause of death among AIDS patients, in the deck's own words
• Invasive aspergillosis and mucormycosis — neutropenia, transplantation, poorly controlled diabetes

Which closes the circle with Unit 26 §6: the AIDS-defining illnesses are the infections controlled by CD4 cells, and half of them are fungal.

Test yourself

What determines whether a mycosis develops? → Primarily the host immune status and environmental exposure, rather than the infecting organism
Name the three fungal virulence factors with examples. → Capsules for antiphagocytosis (Cryptococcus, Histoplasma) · enzymes digesting host cells (keratinase of dermatophytes) · mycotoxins causing poisoning and being mutagenic and carcinogenic
Name the five types of mycosis. → Pathogenic fungal infection · opportunistic fungal infection · hypersensitivity · mycotoxicosis · fungal toxins causing tumours
Name the four levels of pathogenic fungal infection. → Superficial, cutaneous, subcutaneous, dimorphic systemic
Superficial vs cutaneous infection? → Both invade no living tissue, but superficial causes no pathological change or cellular response (patients often unaware), while cutaneous causes skin lesions from irritation and toxic metabolites
Which fungus causes meningitis, and where does it come from? → Cryptococcus neoformans, from soil and pigeon faeces, entering via the lung
Which fungus causes hepatoma, and by what toxin? → Aspergillus flavus, via aflatoxin
Name the opportunistic fungi. → Candida albicans, Cryptococcus neoformans, Aspergillus, Mucor, Pneumocystis carinii

⭐ The deck's own definitions and questions

Slide 52 — five definitions and eight questions

The five definitions

Fungi — eukaryotic, spore-bearing, non-photosynthetic microbes, each cell having at least one nucleus with a nuclear membrane, ER, mitochondria and secretory apparatus, and no chlorophyll.

Hypha — a branching, threadlike filament of fungus that elongates at its tip.

Mycelium — a mass of hyphae collectively.

Fungal spore — the reproductive structure or unit of fungi, sexual (by meiosis) or asexual (by mitosis).

Fungal dimorphism — growth as the yeast (parasitic, tissue, unicellular) form at 35–37 °C or the mould (saprophytic, multicellular) form at 25 °C, depending on redox potential and pH, and related to pathogenicity.

TMU Microbiology — Medical Mycology (52 slides) summary slide

“How many types of mycotic disease are there? What are they?”

Five. A · Pathogenic fungal infection (superficial, cutaneous, subcutaneous, dimorphic systemic) · B · Opportunistic fungal infection · C · Hypersensitivity · D · Mycotoxicosis · E · Fungal toxins causing tumours.