WEEK 4: FUNGI STRUCTURE AND MYCOSES

Question 1

Outline ways in which fungi affect the environment.

Answer 1

1. Beneficial in food production:
   *Bread rising due to yeast activity
   * Cornish Blue Cheese: Penicillium spp. added for flavoring, resulting in ‘blue veins’
   * Edible mushrooms
   * Bread (yeast) spread
2. Fungi metabolites are a source of antimicrobials & other medicines.
3. Contamination of damp areas & food spoilage.
4. They can be agricultural challenge:
   Many fungi spp. are plant parasites.
5. They affect human health: Ring worm, oral thrush, Pulmonary aspergillosis.

*Fungi are increasingly becoming leading pathogens especially amongst immunocompromised patients i.e., cancer, AIDS
*Cause various infections ranging from superficial to invasive.

Question 2

Thallus (body) of fungi is diverse but generally two forms. What are they?

Answer 2

Thallus (body) of fungi is diverse but generally two forms:
Yeasts
Filamentous

Question 3

Describe Yeasts.

Answer 3

*Unicellular fungi
*Reproduceasexually bybudding.
*Round or oval-shaped cells, and they reproduce through a process called budding.
*Growth: Yeasts are known for their ability to grow in liquid or semi-solid environments. They can ferment sugars and produce alcohol and carbon dioxide.
*Ecological Roles: Yeasts have various ecological roles, including being used in baking, brewing, and winemaking, as well as in the production of biofuels and biotechnology.

Question 4

Describe Filamentous

Answer 4

*Multicellular strands termedhypha/ hyphae

• Which can form a mycelium, the vegetative body of the fungus.

THE HYPHAE CAN BE:
-Septate: divided into discreet cells by walls (septa)
-Coenocytic:notdivided by septa, thus forming a continuous tubular network.

*Growth: Filamentous fungi are well-suited for growth on solid substrates. They secrete enzymes that break down complex organic matter into simpler molecules, which are then absorbed for nutrition.

*Reproduction: These fungi can reproduce both sexually and asexually. Asexual reproduction often involves the formation of spores at the tips of specialized hyphae.

*Ecological Roles: Filamentous fungi are ecologically important as decomposers, breaking down dead organic material and recycling nutrients. They also form mutualistic relationships with plants (mycorrhizae) and can be pathogenic, causing diseases in plants and animals.

Question 5

What is meant by that fungi are dimorphic / biphasic?

Answer 5

Unicellular to filamentous transitions influenced by changes in environmental conditions.

Question 6

State 3 major components- ‘polysaccharides’ (90%) that make up the fungi cell wall.

Answer 6

Three major components– :

*Chitin (polymer of N-acetyl-glucosamine-NAG)
*Glucans (polymers of glucose)
*Mannans (chains of mannoses bound to cell wall proteins)

Question 7

State the function of the following components of fungi cell wall:
*Chitin
*Glucan
*Mannan

Answer 7

1. Chitin
   -Providing rigidity and strength to the cell wall, making it resistant to mechanical stress.
   -Acting as a physical barrier, protecting the fungal cell from environmental threats such as osmotic pressure and microbial attack.
   -Facilitating cell division by defining the cell shape and maintaining cell integrity.
2. Glucans
   *Contributing to the rigidity of the cell wall, working in conjunction with chitin.
   *Playing a role in cell adhesion and recognition, which is important for interactions with other cells and host organisms.
3. Mannan
   *Assisting in the recognition and binding of fungi to host cells or substrates.
   *Modulating the host immune response, as the presence of mannan can trigger immune reactions in the host organism.
   *Providing structural support to the cell wall and influencing its permeability.

Question 8

Describe the cell membrane of fungi.

Answer 8

Phospholipid bilayer interspersed with ‘Ergosterol’ (a sterol).
-Ergosterol, key component regulating structural integrity & fluidity.
-Ergosterol not found in mammalian cells, so ideal target of certain antifungal drugs e.g., azoles, polyenes

Question 9

Immediately exterior to cell membrane (minor component)
~1-2% of cell wall in yeasts & 10-20% in filamentous fungi

Long linear polymers of -1,4-linked NAG
Confers enormous tensile strength to cell wall
Unique (also found as component of shells of molluscs e.g. snails)

Synthesized in cytoplasm by chitin synthase (integral membrane enzyme) - target for some anti-fungal drugs.

What structure is described above?

Answer 9

Chitin

Question 10

Main structural polysaccharide (50-60%) to which other cell wall components are attached

Repeating glucose assembled into branched chains linked by -glucosidic linkages (mainly -(1,3)
Other fungal walls may comprise: -(1,3)-glucan & -(1,6)-glucan (mixed) or -(1,4)-glycan or -(1,3)-glucan

Synthesized in cytoplasm by -1,3-glucan synthase, then transported to periplasm.
Glucan synthase target for anti-fungal drugs i.e., echinocandins

What structure is described above?
Where is it found?

Answer 10

Glucans
Cell wall of fungi

Question 11

Oligopolysaccharide of mannose. Diff. types e.g. galactomannan, glucomannan, galactoglucomannan
Fungi cell wall: mannans bound to proteins via N- or O-linkages.

Different Manno-proteins within & across fungal species.

What structure is described above?
Where is it found?

Answer 11

Mannans
Cell wall of fungi

Question 12

State the 2 broad categories of proteins found on the fungi and their functions.

Answer 12

Proteins - 2 broad categories

i) Wall-associated enzymes (WAEs)

ii) Structural proteins

WAEs have catalytic activities: cell wall synthesis & remodeling e.g., chitinases; glucanases; peptidases (breakdown cell wall components) & glycosyltransferases (synthesis & crosslinking cell wall polysaccharides)

Structural proteins: cell migration, adhesion

Question 13

Describe the cell wall of the following different fungi.
*Candida spp.
*Pneumocystis spp.
*Aspergillus spp.
*Aspergillus fumigatus
*Cryptococcus spp
*Histoplasma capsulatum:

Answer 13

Candida spp.: mainly O & N-linked mannans & phosphorylated mannans

b. Pneumocystis spp: lack chitin synthesis enzymes

c. Aspergillus spp.: conidial spore wall has outer hydrophobin layer (rodlets) & inner melanin layer.

d. Aspergillus fumigatus: hyphae have typical inner CW but α-1,3-glucan, galactomannan & galactosaminoglycan in outer CW

e. Cryptococcus spp.: inner layer of melanin; outer thick capsule (inhibits phagocyte function)

f. Histoplasma capsulatum: hyphae have outer layer of α-1,3-glucan that hinders detection by the host immune system.

Question 14

State the function of PRRs.

Answer 14

-Pattern recognition receptors (PRRs) are key elements of the innate immune system & expressed by antigen presenting cells i.e., dendritic cells & macrophages
-Recognize ‘Pathogen Associated Microbial Patterns’ in fungi cell wall

Question 15

Describe fungal nutrition.

State the pH and temperature optimal for growth of fungi even though many can grow in extreme conditions too.

Answer 15

*Diverse: obligate aerobes & facultative anaerobes
*Heterotrophs: obtain carbon from organic matter

Secrete extracellular enzymes, digesting complex organic material into sugars, peptides, amino acids. These are assimilated as sources of carbon & energy.
E.g., decomposers- digest dead animal & plant materials.
E.g., parasites- take up nutrients from living calls of plants & animals.

pH 4-7 & 20-30C optimal for growth. But many can grow in extreme conditions too.

Question 16

Fungi can reproduce in both asexual & sexual phases. Influenced by environmental conditions.

State the 3 main types of fungi asexual reproduction.

Answer 16

3 main types:
*Simple cell division (budding of yeasts)-cell enlarges at one edge, bud forms & new cell breaks free
*Production of spores (conidia) in sporangium (fruiting body)
*Outgrowth of hyphae & fragmentation of mycelium
-Small fragments of mycelium may detach & grow individually
-Fragmentation of parent hyphae into’- asexual spores i.e., arthrospores & chlamydospores

Question 17

Asexual spores vary shape, size, motile or non-motile, thin or thick walled, colorless or pigmented.

State the two main types of asexual spores.

Answer 17

Asexual spores vary shape, size, motile or non-motile, thin or thick walled, colorless or pigmented.

Two main types:
*Sporangiophores
Formed by cleavage of contents in sac-like fruiting body ‘sporangium’ (specialized hyphae) into uninucleate fragments.

*Conidiospores/ conidia
Not within membrane, formed at tips or sides of simple or differentiated – ‘conidiophores.

Question 18

State the 3 phases of sexual reproduction in fungi.

Answer 18

Diverse sexual reproduction processes

Haploid gametes produced in specialized hyphae (‘gametangia’) undergo fusion & produce spores.

Formed within sac (ascus) - ‘ascospores’
On club-shaped structure (basidium) - ‘basidiospores’

Sexual reproduction completed in 3 phases:
Heterokaryogamy
Karyogamy
Meiosis

Question 19

Describe the 3 phases of sexual reproduction in fungi.

Answer 19

Heterokaryogamy:

Heterokaryogamy is the initial phase of sexual reproduction in fungi.
It involves the fusion of two different hyphal cells, often originating from different fungal strains or mating types.
This fusion results in a heterokaryotic cell, where the nuclei from the two different parental cells coexist within the same hyphal compartment. These nuclei are genetically distinct.

Karyogamy:

Karyogamy is the phase during which the nuclei within the heterokaryotic cell fuse to form a diploid nucleus.
In other words, karyogamy involves the fusion of two compatible nuclei, resulting in a diploid state. This is a critical step in the sexual life cycle of many fungi.

Meiosis:

Meiosis is the final phase of sexual reproduction in fungi.
During meiosis, the diploid nucleus produced by karyogamy undergoes two rounds of cell division, reducing the chromosome number by half.
This process generates haploid spores, which are typically enclosed in specialized structures (asci in ascomycetes or basidia in basidiomycetes) and eventually released into the environment.
These haploid spores have the potential to germinate and give rise to new haploid fungal individuals, which may, in turn, undergo heterokaryogamy to start the sexual reproductive cycle anew.

Question 20

Commensal fungus of scalps of most healthy adults, feeds on oils secreted by hair follicles
But
Sometimes grows out of control, irritates scalp, causes skin cells to die, fall off, clumping with oil from hair & scalp
Appear white & flaky in hair or clothes
Associated with dandruff, eczema & other skin diseases

Name the fungus described above.

Answer 20

MalasseziaFungi (Basidiomycota)

Question 21

Virulence factors allow fungal survival, persistence & eventually tissue damage in host.

State 4 virulence factors of fungi.

Answer 21

*Adherence structures: allow attachment to host tissues

*Cause damage of host tissues & impairment of host defenses i.e. production of phospholipases, proteases, elastases (elastin significant component of the lungs, elastases implicated in pulmonary infections i.e. in aspergillosis):

*Ability to reversibly switch to different morphology forms during infection e.g. dimorphic fungi

*Thermotolerance

Question 22

Generally fungi are harmless but some can cause human infections
BUT
Human fungal pathogens have become increasingly important due to increase in nos. of immunocompromised patients i.e., cancer, AIDS.

State the 3 classes of fungal diseases.

Answer 22

Fungal disease may be generally classified into:
*Allergy or hypersensitivity
*Mycotoxins (fungal toxins) i.e. aflatoxins
*Mycosis or growth of fungus on the skin or in the body:

Question 23

What are mycotoxins?

Give examples.

Answer 23

Mycotoxins are toxic compounds produced by various species of fungi.

These compounds can contaminate food, animal feed, and other agricultural products, posing a significant risk to human and animal health.

Mycotoxins are often produced by molds, especially those belonging to the genera Aspergillus, Penicillium, and Fusarium.

Aflatoxins: Produced primarily by Aspergillus flavus and Aspergillus parasiticus, aflatoxins are potent carcinogens and are often found in peanuts, corn, and other crops.

Question 24

State the 4 categories of mycoses.

Answer 24

Mycoses range from superficial lesions to serious life-threatening diseases.

Categories:
*Superficial
*Subcutaneous
*Systemic
*Opportunistic

Question 25

Infections of surface areas of skin, hair/scalp or nails

‘Dermatophytes’- general term for fungi causing these infections

Fungi in skin causes inflammation, pruritus

3 genera are leading causes: Epidermophyton, Microsporum & Trichophyton.

Diseases by these genera referred to as ‘tineas’ (ringworm) of various parts of the body:

T. corporis (body ringworm), T. cruris (groin/ jock itch), T. unguium (nails), T. capitis (scalp), T. barbae (beard/chin)

What is described above?

Answer 25

Superficial mycoses

Question 26

Sporotrichosis: by Sporothrix schenckii
Dimorphic, ubiquitous saprophyte of wood, bark of trees & soil

Occupational hazard of agricultural workers

Transmission: fungal contamination of wounds or abrasion sites

At body TC, conidia germinate into yeasts & cause infection characterised by suppurative, granulomatous cutaneous nodules along local lymphatic channels

Symptoms: nodular lesions/ bumps under skin, may be ulcerous at point of entry or along lymph nodes & vessels

What is described above?

Answer 26

Subcutaneous mycoses

Question 27

Dimorphic fungus common in soil of central & south eastern U.S. A. Endemic in Ohio, Mississipi

Infection can be via wounds: causing disfiguring granulomatous lesions & multiple abscesses in skin & subcutaneous tissue

But mostly transmission is via inhalation of the spores, causing an pulmonary infection presenting as acute pneumonia (which may become chronic)

The infection may disseminate haematogenously & become extrapulmonary. Commonly presenting as subcutaneous skin lesions, becoming ulcerous
But
Can also cause infections in various organs & the CNS

What disease is described above?
What type of mycoses is it?

Answer 27

Blastomyces dermatitidis (Blastomycosis)
Subcutaneous mycoses

Question 28

Serious infections affecting lungs & also other internal organs & blood vessels, generally by inhalation of spores from filamentous fungi (in their natural habitat
E.g. some fungi can also cause thrombosis in blood vessels

Mostly the leading pathogens initially cause a pulmonary infection. But then the infection may then spread, depending on the species to extrapulmonary sites

Leading fungal pathogens include certain species from the:
Aspergillus, Histoplasma, Coccidioides, Blastomyces, Paracoccidioides genera

What is described above?

Answer 28

Systemic mycoses

Question 29

State 3 higher risks factors of invasive fungal lung infections.

Answer 29

Higher risk
*Transplantation procedures e.g., organ; bone marrow; hematopoietic stem cells
*Neutropenia (acute or chronic)
*Colonization by fungi spp. due to:

Use of immune-suppressant agents for inflammatory conditions
&/or antimicrobial prophylactic regimens for immune-suppressed patient groups

Lower risk
-Poorly controlled diabetes results in reduced neutrophil function

Question 30

Describe what happens in Aspergillus fumigatus (Aspergillosis/ farmers lung disease).

Answer 30

Aspergillus fumigatus (Aspergillosis/ farmers lung disease)
Spores inhaled from rotting vegetation or compost may cause clinical allergy or asthma or invasive lower respiratory tract infection.

Mycelium may grow large enough to be seen on X-ray i.e., fungus ball/ aspergilloma, which may cause asphyxiation.

In susceptible host: after inhalation of airborne conidia (ideal size for alveolar deposition) there is germination of conidia into hyphae in alveoli causing invasive disease

Question 31

Outline virulence factors of Aspergillus species.

Answer 31

*Conidia bind to human fibrinogen & laminin: vital step allowing adherence to host tissues

*Hyphae produce proteases which degrade fibrinogen & laminin

*Elastases: serine protease & metalloprotease: degradative activity against ‘elastin’-constitutes 30% lung tissue

*A. fumigatus also produces gliotoxin: inhibits macrophage phagocytosis &T cell activation

Question 32

Indigenous in U.S.A. especially in warm, arid regions e.g. Ohio, Mississippi River valleys
Also called ‘Valley Fever’
Highly infectious, self-limiting
Lives in soil & cause respiratory disease
Infection is by inhaling airborne spores that germinate & grow’ in lungs. Few develop disseminated disease. But when this happens, the infection may also affect the skin, soft tissues bones & CNS (meningitis most serios complication, without treatment it is fatal)

What is described above?

Answer 32

Coccidioidomycosis: C. immitis & C. posadasii

Question 33

Endemic in certain regions of U.S.A - Ohio, Mississipi, Ottawa river valleys
Affecting >80% young adults from states bordering Ohio & Mississippi rivers
Fungus associated soils with high concentration of bird & bat droppings
Inhalation of airborne spores: germinate in lungs causing pneumonia like symptoms hepatic infection may also occur (also infections in the spleen, bones may occur

What is described above?

Answer 33

Histoplasmosis: Histoplasma capsulatum

Question 34

Common cause of meningitis in immunocompromised adults & can also cause lung infections or pneumonia

*Clinically relevant to Botswana: meningitis in AIDS patients (AIDS defining illness)

Frequently found in soil containing bird droppings (high conc. in bird faeces)

Clinically important species
C. neoformans
C. gattii

What is described above?

Answer 34

Cryptococcus neoformans Cryptococcosis

Question 35

What is the virulence factor for C. neoformans?

Answer 35

Encapsulated budding yeast, becoming thickly encapsulated in mammalian tissues
Capsule: viscous polysaccharide composed primarily of glucuronoxylomannan

Capsule envelopes cell wall, thus phagocytes cannot bind via mannose & -glucan receptors & yeast subverts phagocytosis
Its been observed that antibodies to C. neoformans glucuronoxylomannan may be present in serum but opsonization of yeast cells fails & no resultant phagocytosis occurs

2. Melanin synthesis: can occur in C. neoformans cell wall:

Antimicrobial oxidants produced by phagocytes e.g. superoxide anions & singlet oxygen. BUT

Melanins are scavengers of reactive O2 intermediaries, thus organisms producing them become relatively resistant to leukocyte attack

3.

Question 36

Causes severe, often fatal pneumonia (Pneunocystis pneumonia-PCP) in immunocompromised individuals i.e. HIV & AIDS
Difficult to study because P. jiroveci cannot be cultured outside of host. Not easily obtained as few organisms present in upper respiratory tract secretions

Invasion & inflammation of lungs, causes epithelium to rupture & alveoli septa to thicken

Foamy exudate collects in alveoli but can also cause extrapulmonary infections especially in immunocompromised.

What is described above?

Answer 36

Pneumocystis jiroveci (previously Pneumocyctis carinii)

Question 37

State 2 opportunustic fungal infections

Answer 37

1. Candida albicans
2. Mycormycosis

Question 38

Aetiology: diff. fungi species of the order Mucorales: Commonly caused by Rhizopus oryzae & Mucor spp. (also Lichtheimia spp & Rhizomucor spp.)
Transmission: inhalation of mucormycete spores, causing infections in sinuses & lungs, which can then spread throughout the body

RARE but life threatening. Mostly affects immunocompromised patients.**Risk factor – Diabetes (uncontrolled) &neutropenia

What type of Mucormycosis is described below?

1. Black lesions on nasal bridge or upper portion of oral cavity. Fever
2. Fever; cough; chest pains; shortness of breath
3. Blisters or ulcers on skin which can turn black
4. Systemic, can reach brain & cause coma

Answer 38

1. Rhinocerebral mycosis (sinus and brain)
   Black lesions on nasal bridge or upper portion of oral cavity. Fever
2. Pulmonary mucormycosis
   Fever; cough; chest pains; shortness of breath
3. Cutaneous mucormycosis
   Blisters or ulcers on skin which can turn black
4. Disseminated mucormycosis
   Systemic, can reach brain & cause coma.

Question 39

Describe candidiasis as an opportunistic fungal infection.

Answer 39

Candidiasis- primarily by Candida albicans
Dimorphic - oval budding yeast on mucosal surfaces; normal flora of intestinal & urogenital tracts. BUT invasive strains – form hyphae

Superficial candidiasis ‘thrush’ – milky/ white patches of inflammation in mucous membranes i.e. mouth, vagina. Opportunistic infections especially in infants, diabetic patients, debilitated patients & those on prolonged antibiotic therapy

**In HIV-infected patients candidiasis of the oesophagus is regarded an AIDS-defining illness.

NOTE: C. albicans and non-albicans Candida spp. can also cause systemic infections in immunocompromised patients i.e. neutropaenic patients. The invasive candidiasis incl. endopthalmitis, disseminated candidiasis