Pathogenic Fungi (12-13)

Question 1

What are the properties of fungi?

Answer 1

Fungi are eukaryotic adidas → include yeasts, moulds and fleshy fungi
Have a rigid cell wall → consisting of layers of polysaccharides, forms a rigid matrix
Chemoheterotrophs → require organic compounds for both carbon and energy sources
Obtain nutrients as saprophytes (live off of decaying matter) or as parasites (live off living matter) → are recyclers
Some stimulate the plant roots to proliferate
Lichens → composed of fungi and a photosynthetic component - either a eukaryotic alga or a cyanobacterium
Disease causing bacteria → infect mostly skin, hair and nails - able to hydrolyse keratin a tough protein found in dead skin cells and nails
Several fungal pathogens can cause lung infections
Asperigillus species → produce a toxic compound called aflatoxin which causes liver cancer
Ergot → the active ingredient in the hallucinogenic drug LSD is produced by fungi

Question 2

What is the effect of fungi in industry?

Answer 2

Used by industry to produce a variety of products → due to ability of recycling nutrients, produce enzymes which can degrade some matter
However, can cause undesirable economic effects → e.g. spoilage of fruits, grains and vegetables, destruction of wood and leather products
Over 100,000 species of fungi, only ~100 are pathogenic for animals

Question 3

What kingdoms to fungi fit into?

Answer 3

Chromistan fungi → pseudo (non-tree) fungi with cellulosic hyphal walls - Phyla, Oomycota and Hyphochytriomycota
Eumycotan fungi → true fungi with chitinous hyphal walls - Phyla, Chytridiomycota, Zygomycota, Glomeromycota, Dikaryomycota

Question 4

What are the 3 major mechanisms fungi can cause disease through?

Answer 4

Hypersensitivity → by causing immune responses that result in allergic reactions following exposure to specific fungal antigens
Toxins → by producing toxins e.g. mycotoxins - a large diverse group of fungal exotoxins
Infection → the growth of fungus on or in the body is a mycosis

Question 5

What are the different groups of fungi that can cause disease?

Answer 5

Dermatophytes → a few fungi have evolved ability to attack the outer surface of human beings
Normally soil organisms → adapted to life in the unusual and rather hostile environment of the human body, often responding to this environment by developing a different morphology (thermal dimorphic saprobes)
Opportunistic saprobes → attack us only when our defences are down - when our immune system are diseased or deficient, or when artificially suppressed

Question 6

What are the 3 main types of human fungal infections?

Answer 6

Cutaneous (superficial) mycoses → involve the outer layers of the skin and cause an allergic or inflammatory response
→ treatable - topical fungicides
Subcutaneous mycoses → involve fungi of low inherent virulence which have been introduced to the tissues through a wound of some kind
→ remain localised or spread only by direct mycelial growth
→ still treatable (more difficult) but give rise to more damaging lesions
Systemic mycoses → caused by either true pathogenic fungi which can establish themselves in normal hosts
→ or by opportunistic saprobic fungi which could not infect a health host, but can attack individuals whose immune system is not working
→ both kinds sometimes become widely disseminated through the body of the host
→ typically pulmonary - cause serious disease, inhalation of spores

Question 7

What are the types of cutaneous (superficial) mycoses?

Answer 7

Superficial cosmetic fungi infections → skin or hair shaft where no living tissue is invaded and there is no cellular response from the host - no pathological changes are elicited e.g. dandruff caused by Malassezia furfur
More commonly superficial fungal infections of the skin, hair or nails → group of closely related mould fungi called dermatophytes
→ can colonise and digest keratin - a variety of pathological changes occur in the host because of the presence of the infectious agents and its metabolic products

Question 8

What is ringworm?

Answer 8

A type of cutaneous mycoses also referred to as Tinea infections → e.g. Tinea pedis (feet) or Tinea capitis (scalp)
Caused by 20 species of dermatophyte fungi → 3 genera Trichophyton, Microsporum & Epidermophyton
Infections spread by direct or indirect contact with infected individual or animal → e.g. fragment of certain containing viable fungus (direct), floor of swimming pool, shower, combs (indirect)
→ spread through fungal spores - good for transmission, long living
Dermatophytes have ability to utilise keratin as a nutrient source → they invade keratin via enzymic digestion (keratinise) and mechanical pressure

Question 9

Why is the disease process for ringworm unique?

Answer 9

1. No living tissue is invaded → the keratinised stratum corner is simply colonised
   → however, the presence of the fungi and its metabolic products usually induces an allergic and inflammatory response in the host - type and severity related to the species and strain of dermatophyte
2. Dermatophytes are the only fungi that have evolved a dependency on human or animal infection for the survival and dissemination of their species

Question 10

What causes Tinea Pedis infection?

Answer 10

The shedding of skin scales containing viable infectious hyphal elements (arthroconidia) of the fungus (e.g. *T. rubrum)
→ scales may remain infectious in the environment for months or years, thus transmission may take place by indirect contact long after infective debris have been shed
→ substrates like carpet and matting that hold skin scales are good vectors

Question 11

How are Tinea infections treated and prevented?

Answer 11

Topical therapy → usually fine for skin infections but oral antifungals e.g. fluconazole, are required for extensive skin infections or those of the nail or scalp
Prophylatic use of anti fungal foot powder → after bathing helps reduce the spread of infection among swimmers

Question 12

What is fluconazole?

Answer 12

A widely used bis-triazole anti fungal agent
→ has 5-membered ring structure containing 3 nitrogen atoms

Action → inhibition of cytochrome P450 14a-demethylase - an enzyme in the sterol biosynthesis pathway that leads from lanosterol to ergosterol (as essential component of the fungal cytoplasmic membrane)

Question 13

What are the properties of yeast?

Answer 13

Unicellular fungi → usually appear as oval cells 1-5um wide by 5-30um long
Have typical eukaryotic structures
Facultative anaerobes → get their energy through aerobic respiration as well as fermentation
Have a thick polysaccharide cell wall
Can cause superficial and systemic infections

Question 14

How does the immune system respond to yeast?

Answer 14

Components of the yeast cell wall (PAMPs) bind to pattern-recognition receptors on a variety of defense cells
→ triggers innate immune defences such as inflammation, fever and phagocytosis
→ can also activate the alternative complement pathway and the lectin pathway

Question 15

What allows yeast Candida albicans to invade deeper into tissues?

Answer 15

Pseudohyphae (branching filaments of attached elongated yeast cells) help the yeast to invade deeper tissues after it colonises the epithelium
→ in addition to its usual oval budding, is also able to produce pseudohyphae - buds elongate forming a tube-like structure called a germ tube which remain attached to one another eventually producing a filament called a pseudohypa

Question 16

How do yeast reproduce?

Answer 16

Asexually by a process called budding
→ a bud is formed on the outer surface of the parent cell as the nucleus divides
→ one nucleus migrates into the elongating bud, cell wall material forms between the bud and the parents cells and the bud breaks away

Sexually → by means of sexual spores called ascospores
→ result from fusion of the nuclei from two cells followed by meiosis - recombination
→ less common than aseual but allows for genetic recombination

Question 17

Where is Candida albicans usually found?

Answer 17

As normal flora not he mucous membranes and in the GI tract
→ usually held in check by 1) normal flora bacteria, 2) normal body defences

Can cause a variety of opportunistic infection in people who are debilitates, immunosuppressed or have received prolonged antibacterial therapy
→ women who are diabetic, pregnant, taking oral contraceptives, or having menopause are more prone to vaginitis - these conditions alter the sugar conc and pH of the vagina making it more favourable for the growth of Candida

Question 18

What is candidiasis?

Answer 18

Any Candida infection → most commonly causes vaginitis - inflammation of the mucous membranes of the vagina, thrush - infection of the mucous membranes of the mouth, balantitis - lesions on the penis from a female with vaginitis and cutaneous infections - infections of moist skin or the nail beds
→ less commonly can infect the lungs, blood, heart and meninges (the membranes covering the brain and spinal cord) - especially in the compromised or immunosuppressed host
→ also causes 10% of all cases of septicaemia - where microorganisms enter the bloodstream

Question 19

How are Candida infections diagnosed?

Answer 19

1. Collect samples → from skin (using blunt scalpel) from the edges of the lesions - where the most viable fungus is likely to be
   → from the mouth or vagina from areas of white plaques
2. Direct microscopy → examination specimens for the presence of small, round to oval, thin-walled clusters of budding yeast cells and branching pseudohyphae - providing the clinical manifestations support the diagnosis

Question 20

How are Candida infections treated and prevented?

Answer 20

Correct underlying conditions that allows it to colonise the skin or mucosa → i.e. restore the normal epithelial barrier function
Cutaneous candidiasis → control of excessive moisture, heat and friction which cause local skin maceration and treatment with a topical imidazole compound
Oral candidiasis → nystatin, amphotericin B or miconnazole are effective - azoles prevent the synthesis of ergosterol
→ polyenes (e.g. amphotericin B and nystatin) interferon with the integrity of the fungal cell membrane by binding to membrane sterols
Most cases of vaginal candidiasis can be treated with a topical imidazole or the oral fluconazole
Oral treatment is essential for the treatment of intractable chronic infections → prolonged therapy may be required and development of resistance can occur

Question 21

What is chromoblastomycosis?

Answer 21

A subcutaneous mycoses → chronic localised disease of the skin and subcutaneous tissues
→ causative organisms: *Cladophialophora sp., Fonsecasea sp., Phialophora sp.)
→ infections caused by the traumatic implantation of fungal elements into the skin and are chronic, slowly progressive and localised
→ characterised by crusted, warty lesions usually involving the limbs
→ world-wide distribution but more commonly in bare footed populations living tropical regions

Question 22

How is chromoblastomycosis diagnosed and treated?

Answer 22

Diagnosis → presence in skin scrapings and/or biopsy tissue of brown pigmented, planate-dividing, round sclerotic bodies from a patients supporting clinical symptoms
Treatment → surgical removal of tissue (though required removal of a margin of unaffected tissue to prevent local dissemination)
→ fluorocytosine (a pyrimidine analog) and the azaleas thiabendazole and itraconazole are effective

Question 23

What is sporotrichosis?

Answer 23

A subcutaneous mycoses → primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and adjacent lymphatics
→ characterised by nodular lesions which may ulcerate
→ infections caused by the dramatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs - more serious, non-specific symptoms
→ secondary spread to joints, bond and muscle is not infrequent and the infection may also involve the CNS, lungs or genitourinary tract

Question 24

How is sporotrichosis diagnosed and treated?

Answer 24

Diagnosis → tissue biopsy will contain very low numbers of narrow base budding yeast cells
Treatment → cutaneous lesions respond well to saturated potassium iodide, - itraconazole and terbinafine can also be effective

Question 25

What is terbinafine?

Answer 25

A type of synthetic anti-fungal agent → an allylamine
→ highly lipophilic in nature and tends to accumulate in skin, nails and fatty tissues

Action → inhibits ergosterol biosynthesis via inhibition of squalene epoxidase - enzyme part of the fungal sterol synthesis pathway for the fungal cell membrane

Question 26

What is Cryptococcus neoformans?

Answer 26

A serious pathogenic yeast → can cause systemic mycoses
→ yeast can also reproduce sexually - sexual form called Filobasidiella neoformans
→ appears as an oval yeast, forms buds with a thin neck and is surrounded by a thick capsule (enables it to resist phagocytic engulfment) - does not produce pseudphyphae and chlamydospores
→ infections usually mild or subclinical, but when symptomatic usually begin in the lungs after inhalation of the yeast in dried bird faeces
→ found in soil, actively grows in the bird faeces but not in the bird itself
→ usually infection doesn’t process beyond the pulmonary stage - but in immunosuppressed it may spread through the blood to the meninges and other body areas causing cryptococcal meningoencephalitis (often fatal)
→ cutaneous and visceral infections also found

Question 27

What is the infectious cycle of C. neoformans?

Answer 27

Reside in environment and has been found associated primarily with pigeon droppings
Infection of humans generally occurs when basidiospores produced by it in the nature are inhaled into the lungs
→ inhaled spores are deposited into the alveoli and germinate to establish a dormant infection or disseminate the CNS
→ once dissemination has occurred, viable cells can be culture from the cerebrospinal fluid of affected individuals

Question 28

What is Pneumocystis carinii?

Answer 28

Can cause systemic mycoses
→ thought to be transmitted from person to person by the respiratory route and is almost always asymptomatic
→ in persons which highly depressed immune responses e.g. leukemias or HIV can cause an often lethal pneumonia called PCP

Question 29

What is blastomycosis?

Answer 29

Disease caused by the dimorphic fungus Blastomyces dermatitidis → can cause systemic mycoses
Endemic in the southeastern and south central states of North America
→ outbreaks associated with occupational or recreation activities around streams or rivers which high content of moisture soil enriched with organic debris and/or rotting wood
Infection if acquired via inhalation of the conidia which transforms into the yeast form once in the lungs
After 30-45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur

Question 30

What is histoplasmosis?

Answer 30

Condition caused by infection with the dimorphic endemic fungus Histoplasma capsulatum → can cause systemic mycoses
Most common cause of fungal infections in the world
→ majority of acute cases of infection with this fungus follow a subclinical and benign course in normal hosts
Fatal in immunosuppressed individuals, children <2, the elderly and people exposed to a very large inoculum
Infection acquired through inhalation of microconidia → thus lungs are the most frequently affected site and chronic pulmonary disease may occur
→ frequently associated with pre-existing chronic lung diseases like emphysema

Question 31

What is aspergillosis?

Answer 31

Broad range of disease states whose etiologic agents are membrane of the genus Aspergillus
→ ubiquitous organisms, progressively associated with a growing spectrum of infections in immunocompromised hosts
→ Aspergillus fumigatus → responsible for over 90% of cases of invasive aspergillosis
Three most prevalent diseases: allergic bronchopulmonary aspergillosis, pulmonary aspergilloma and invasive aspergillosis

Question 32

What is allergic bronchopulmonary aspergillosis?

Answer 32

Produces an allergy to the spores of Aspergillus moulds
→ common in asthmatics and cystic fibrosis patients
Symptoms: intermittent eposides of feeling unwell, coughing and wheezing, cough up brown-coloured plugs of mucus
Diagnosis: X-ray or by sputum, skin and blood tests
Long term → can lead to permanent lung damage (fibrosis) if untreated

Question 33

What is Aspergilloma?

Answer 33

Disease in which Aspergillus grows within a cavity of the lung which was previously damages during an illness e.g. tuberculosis - burns into scar from previous problem
→ any lung diseases which cause cavities leave people vulnerable
→ spored penetrate the cavity and germinate forming a fungal ball
Illness caused by secretion of toxins/other products (elastase, proteases)
Symptoms: maybe none early on, weight changes, chronic cough, brain fog, feeling rundown, coughing of blood
Diagnosis: X-rays, scans of lungs and blood tests

Question 34

What is invasive aspergillosis?

Answer 34

Often fatal - no good diagnostic test, often treatment has to be started when the condition is only suspected
→ usually clinically diagnosed in people with low defences e.g. bone marrow transplant, cancer patients, AIDs or major burns - rare inherited condition that gives people low immunity (chronic granulomatous disease - phagosomes inefficient killers)
Symptoms: fever, cough, chest pain, breathlessness - don’t respond to normal antibiotics
Diagnosis: bronchoscopy - inspection of the inside of the lung with a small tube inserted via the nose, X-rays and scans usually abnormal but can help localise the disease

Question 35

What is the treatment and control used against systemic pathogenic fungi?

Answer 35

Effective chemotherapy against systemic fungal infections is very difficult
Amphotericin B → one of the most effective antibiotics - binds to membrane sterols and affects the integrity of the fungal cell membrane, punches holes
→ can give rise to serious side effects e.g. kidney toxicity
Exposure of fungi can rarely be eliminated using air filtration in restricted local environment

Question 36

What contributes to fungal pathogenicity?

Answer 36

Fungal virulence factors can be divided into 2 categories
1 → virulence factors that promote fungal colonisation of the host
2 → virulence factors that damage the host

Question 37

What are virulence factors that promote fungal colonisation?

Answer 37

Adherence → the ability to adhere plays a role in fungal virulence
Capsules → some fungi produce capsules allowing them to resist phagocytic engulfment
→ e.g. yeast Crytococcus neoformans
Cytokines → Candida albicans stimulates the production of cytokine GM-CSF - surpassed the production of complement by monocytes and macrophages
→ can also acquire iron from red blood cells
Resistance → some fungi are resistant to phagocytic destruction
→ e.g. more difficult for phagocytes to engulf Candida albicans when its in pseudohyphal form

Question 38

What are some fungal virulence factors that damage the host?

Answer 38

Enzymes → as fungi grow in the body they can secrete enzymes to digest cells
→ in response to the fungus and cell injury cytokines are released - leads to inflammation and extracellular killing by phagocytes causing further destruction of host tissues
Mycotoxins → many moulds secrete mycotoxins (common when growing on grains, nuts and beans) - may cause a variety of effects in humans and animals if ingested e.g. loss of muscle coordination, weight loss and tremors, some are mutagenic and carcinogenic
→ aflatoxins are especially carcinogenic
→ mycotoxin symptoms: dermatitis, inflammation of mucous membranes, cough, fever, headache and fatigue