dave (L14-15)

Question 1

types of fungi

Answer 1

yeasts
moulds
fleshy fungi

Question 2

fungal pathogen mycology

Answer 2

• eukaryotic
• rigid cell wall (polysaccharides and rigid matrix)
• chemoheterotrophs (organic compounds0
• get nutrients as saprophytes (dead matter) or as parasites (living matter)
• are recyclers
• stimulate the plant roots to proliferate (microisofungi)
• lichens composed of fungi and photosynthetic component (like eukaryotic alga or cyanobacterium)
• Disease-causing fungi: Infect mostly skin, hair, and nails (can hydrolyse keratin)
• cause lung infections
• aflatoxin causes liver cancer
• ergot (in LSD) is produced by fungi

Question 3

how many species are pathogenic for animals?

Answer 3

Of the over 100,000 species of fungi, only about 100 species are pathogenic for animals.

Question 4

benefit and disadvantage of fungi

Answer 4

They play a major role in the recycling of nutrients by their ability to cause decay and are used by industry to produce a variety of useful products.

However, they also cause many undesirable economic effects such as the spoilage of fruits, grains, and vegetables, as well as the destruction of unpreserved wood and leather products

Question 5

fungal lineages

Answer 5

fungal lineages are split into 2 diff types - chromista and eumycota

The Archaebacteria and the Eubacteria
are prokaryotes.

Eukaryotes encompass the other five Kingdoms: Protista (protozoa), Chromista, Plantae, Animalia and Eumycota

Question 6

which kingdoms do fungi fit in?

Answer 6

Fungi have several distinguishing features:

• are eukaryotic (cells have nuclei)
• heterotrophic (can’t make their own food)
• osmotrophic (absorb, don’t ingest, food)
• develop a rather diffuse, branched, tubular body (radiating hyphae making up mycelia or colonies)
• reproduce by means of spores

THEREFORE
this describes, not a single phylogenetic line, but rather a way of life shared by organisms of different evolutionary backgrounds

Question 7

phytophthora

Answer 7

most molds are important plant pathogens and encompass an organism called phytophthora
irish potato famine (1840s) - they ate 6kg of potatoes per person per day
10 years after the infection, the population went from 8 million people to 4 million people

Question 8

define the chromistan and eumycotan fungi

Answer 8

Chromistan fungi (pseudofungi with cellulosic hyphal walls - Phyla Oomycota and Hyphochytriomycota) as well as

Eumycotan fungi (true fungi with chitinous hyphal walls - Phyla Chytridiomycota, Zygomycota, Glomeromycota, Dikaryomycota).

Question 9

human fungi pathogens

Answer 9

about 100 species of fungi infect animals, and only 50 infect us

most fungi are harmless to humans.
Only about 50 species cause human disease
The overall incidence of serious fungal infections is relatively low though certain superficial fungal infections are quite common

Question 10

Fungi cause disease through three major mechanisms

Answer 10

1) by causing immune responses that result in ALLERGIC (hypersensitivity) reactions following exposure to specific fungal antigens
2) by producing TOXINS e.g. mycotoxins – a large diverse group of fungal exotoxins. Aspergillus flavus (which commonly grows on improperly stored food such as grain) produces aflatoxins – which induce tumours in birds feeding on contaminated grain
3) by INFECTION. The growth of a fungus on or in the body is a mycosis

Question 11

the 3 different groups of fungi that cause specific fungal infections / diseases

Answer 11

dermatophytes have a specific ability to attack the outer surface of human beings.

Other fungi cause disease in people and are normally soil organisms, but have also 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 can attack us only when our defences are down - when our immune systems themselves are diseased or deficient, or when we artificially suppress them e.g. to prevent the rejection of transplanted organs.

Question 12

Three main types of human fungal infections (mycoses)

Answer 12

(1) cutaneous (superficial) mycoses, which involve the outer layers of the skin and cause an allergic or inflammatory response;
(2) subcutaneous mycoses, usually involving fungi of low inherent virulence which have been introduced to the tissues through a wound of some kind, and which remain localized or spread only by direct mycelial growth
(3) systemic mycoses, which are caused, either by true pathogenic fungi which can establish themselves in normal hosts, or by opportunistic saprobic fungi which could not infect a healthy host, but can attack individuals whose immune system is not working or is compromised. Both kinds of fungi sometimes become widely disseminated through the body of the host.

Question 13

pathogenic fungi and the diseases they form

Answer 13

TABLE IN L14 S10

Question 14

names of cutaneous (superficial mycoses)

Answer 14

(tinea - medical name for a group of related skin infections)

Tinea capitis ‘ringworm’ Trichophyton tonsurans

Tinea cruris (jock itch or crotch rot) Epidermophyton floccosum

Epidermophyton floccosum - before and after treatment

Tinea pedis : “athlete’s foot. Due to infection with Trichophyton rubrum

ringworm

Question 15

names of Subcutaneous infections

Answer 15

(fungal infection is burying itself beneath the skin and causes more extensive damage)

Chromoblastomycosis

Sporotrichosis

Question 16

names of systemic infections

Answer 16

Histoplasma capsulatum, cause of histoplasmosis

Disseminated coccidioidomycosis
Coccidioides immitis

North American blastomycosis:
Blastomyces dermatitidis

Question 17

superficial cosmetic fungal infections

Answer 17

Cutaneous (superficial) mycoses also include superficial cosmetic fungal infections of the skin or hair shaft where no living tissue is invaded and there is no cellular response from the host. Essentially no pathological changes are elicited e.g. dandruff caused by Malassezia furfur.

More commonly they refer to superficial fungal infections of the skin, hair or nails caused by a group of closely related mould fungi dermatophytes which can colonise and digest keratin
A variety of pathological changes occur in the host because of the presence of the infectious agent and its metabolic products

Question 18

ringworm (also called tinea pedis, or tinea capitis)

- caused by / spread by -

Answer 18

• infections are caused by 20 species of dermatophyte fungi

- Infections spread by direct or indirect contact with an infected individual or animal

Question 19

Disease process of ringworm is unique for two reasons

Answer 19

i) no living tissue is invaded; the keratinised stratum corneum is simply colonised. However, the presence of the fungus and its metabolic products usually induces an allergic and inflammatory response in the host. The type and severity of the host response is often related to the species and strain of dermatophyte causing the infection.
ii) the dermatophytes are the only fungi that have evolved a dependency on human or animal infection for the survival and dissemination of their species

Question 20

dermatophytes using keratin: define tinea pedis

Answer 20

tinea pedis is caused by T rubrum
sub clinical infection shows mild maceration
severe infection shows extensive maceration

keratinase - produced enzyme that degrades keratin in the skin
spores puncture the skin - mechanical pressure but the skin then germinates and colonise
problem - very easy to catch them
spores can stay viable in the env for a very long time

Question 21

infection of T pedis

Answer 21

• usually caused by the shedding of skin scales containing viable infectious hyphal elements [arthroconidia] of the fungus.
• Scales may remain infectious in the environment for months or years. Therefore transmission may take place by indirect contact long after the infective debris has been shed.
• Substrates like carpet and matting that hold skin scales make excellent vectors.

Question 22

Treatment & Prevention of Tinea infections

Answer 22

Topical therapy (i.e. local therapy e.g. creams applied directly to the skin) is usually fine for skin infections but oral antifungals e.g. fluconazole, are required for extensive skin infections or those of the nail or scalp

Prophylactic use of antifungal foot powder after bathing helps to reduce the spread of infection among swimmers (though antiseptic foot baths in swimming pools are commonly of no value)

Fluconazole is a widely used bis-triazole antifungal agent. As with other triazoles, it has five-membered ring structures containing three nitrogen atoms.

Question 23

Mechanism(s) of FLUCONAZOLE action

Answer 23

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

many of fungal agents are azoles (active agent of fluconazole)
they work by inhibiting the cell wall synthesis in the fungi
these are specific to the fungi which is why it is good treatment
many azoles work in similar ways, by inhibiting cell wall biosynthesis of the fungi

Question 24

YEASTS MORPHOLOGY (cause superficial and systemic infections)

Answer 24

a. are unicellular fungi which usually appear as oval cells (1-5 µm wide by 5-30 µm long)
b. They have typical eukaryotic structures
c. Are facultative anaerobes: get their energy through aerobic respiration as well as fermentation.
d. They have a thick polysaccharide cell wall.

Question 25

how does the body protect against infection

Answer 25

one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to micro-organisms that are not associated with human cells.

Question 26

define pathogen-associated molecular patterns

Answer 26

the body detects the presence of microorganisms (not associated with human cells) called pathogen-associated molecular patterns

Components of the yeast cell wall bind to pattern-recognition receptors on a variety of defense cells of the body and triggers innate immune defenses such as inflammation, fever, and phagocytosis.

Yeast cell wall components also activate the alternative complement pathway and the lectin pathway, defence pathways that play a variety of roles in body defence

Question 27

Yeast Candida albicans

Answer 27

in addition to its usual oval budding form, is also able to produce pseudohyphae

Buds elongate forming a tube-like structure called a germ tube.

The elongated buds remain attached to one another and eventually produce a filament called a pseudohypha because it resembles the hypha (a long filament of cells) of a mould

Question 28

use of the pseudohyphae to yeast

Answer 28

The pseudohyphae help the yeast to invade deeper tissues after it colonizes the epithelium.

Since Candida is able to grow as a yeast as well as in a pseudohyphal form it is said to be DIMORPHIC i.e. it has two growth forms yeast-like and mould-like.

Question 29

characteristics of pseudohyphae, blastospores and chlamydospores

Answer 29

Pseudohyphae:Branching filaments of attached, elongated yeast cells resembling the hyphae of moulds

Blastospores: asexual reproductive spores

Chlamydospores: thick-walled survival spores

Question 30

asexual reproduction of yeasts

Answer 30

Yeasts reproduce 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 parent cell and the bud breaks away.

Question 31

sexual reproduction of yeasts

Answer 31

Yeasts can also reproduce sexually by means of sexual spores called ascospores which result from the fusion of the nuclei from two cells followed by meiosis

Sexual reproduction is much less common than asexual reproduction but does allow for genetic recombination

can become more genetically diverse - can infect more species, more easily etc

Question 32

YEAST INFECTIONS

Answer 32

LEARN L14 S22

VERY. VERY IMPORTANT.

Question 33

Oropharyngeal candidiasis

Answer 33

Oropharyngeal candidiasis: includes thrush

Clinically, white plaques that resemble milk curd form on the buccal mucosa and less commonly on the tongue, gums, the palate or the pharynx. Symptoms may be absent or include burning or dryness of the mouth, loss of taste, and pain on swallowing

Question 34

Cutaneous candidiasis

Answer 34

Cutaneous candidiasis: includes “Nappy rash” candidiasis

can occur between the fingers or toes, or in the groin

“Nappy rash” candidiasis is common in infants under unhygienic conditions of chronic moisture and local skin maceration associated with irritation due to irregularly changed unclean nappies

Question 35

Vaginal candidiasis

Answer 35

• a common condition in women
• often associated with the use of broad-spectrum antibiotics, the third trimester of pregnancy, low vaginal pH and diabetes mellitus
• sexual activity and oral contraception may also be contributing factors and infections may extend to include the vulva and the cervix.
• symptoms include intense itching, burning or soreness and production of a creamy white, curd-like discharge.
• chronic refractory vaginal candidiasis, associated with oral candidiasis, may also be a presentation of HIV infection or AIDS

Question 36

Diagnosis of Candida infections

Answer 36

i) Collect samples
from skin (using a blunt scalpel) from the edges of the lesions (where most viable fungus is likely to be)
from mouth or vagina from areas of white plaques

ii) Direct microscopy
Examine specimens for the presence of small, round to oval, thin-walled clusters of budding yeast cells (blastoconidia) and branching pseudohyphae (the finding of just budding yeast cells in such material is of little diagnostic importance – it may have occurred between sample collection and processing) provided the clinical manifestations support the diagnosis

Question 37

Treatment & Prevention of Candida infections

Answer 37

Correct the underlying conditions that allow Candida to colonise the skin or mucosa i.e. to restore the normal epithelial barrier function.

For cutaneous candidiasis: control of excessive moisture, heat and friction which cause local skin maceration and treatment with a topical imidazole compound is usually effective

For oral candidiasis nystatin, amphotericin B or miconazole are effective

• Azoles prevent the synthesis of ergosterol
• Polyenes (e.g. amphotericin B and nystatin) interfere with the integrity of the fungal cell membrane by binding to membrane sterols
• Most cases of vaginal candidosis can be treated with a topical imidazole or the oral fluconazole

Oral treatment is essential for the treatment of intractable chronic Candida infections. Prolonged therapy may be required and development of resistance e.g. to fluconazole can occur.

Question 38

TYPES OF SUBCUTANEOUS MYCOSES

Answer 38

I Chromoblastomycosis

II Sporotrichosis

Question 39

I Chromoblastomycosis (subcutaneous mucoses)

Answer 39

a chronic localised disease of the skin and subcutaneous tissues
(causative organisms are Cladophialophora sp. Fonsecaea sp., Phialophora sp.)

infections are 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 common in bare footed populations
• living in tropical regions

Question 40

I chromoblastomycosis diagnosis and treatment

Answer 40

Diagnosis : presence in skin scrapings and/or biopsy tissue of brown pigmented, planate-dividing, rounded sclerotic bodies from a patient with supporting clinical symptoms

Treatment: Can involve surgical removal of tissue (though requires removal of a margin of uninfected tissue to prevent local dissemination) Fluorocytosine (a pyrimidine analog) & the azoles thiabendazole & itraconazole are effective (can require treatment for 6 to 12 months)

Question 41

II Sporotrichosis

Answer 41

Primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and adjacent lymphatics

Characterized by nodular lesions which may ulcerate.

Infections are caused by the traumatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs.

Secondary spread to joints, bone and muscle is not infrequent, and the infection may also occasionally involve the central nervous system, lungs or genitourinary tract

Question 42

Pulmonary sporotrichosis

Answer 42

Pulmonary sporotrichosis: is rare; usually caused by the inhalation of conidia. Symptoms are non-specific and include cough, sputum production, fever, weight loss and upper-lobe lesion. Haemoptysis (coughing up blood) may occur and it can be massive and fatal. The natural course of the lung lesion is gradual progression to death

Question 43

Pulmonary sporotrichosis diagnosis and treatment

Answer 43

Diagnosis : Tissue biopsy will contain very low numbers of narrow base budding yeast cells (2-5um)

Treatment: Cutaneous lesions respond well to saturated potassium iodide
itraconazole & terbinafine have also proved to be effective

Question 44

Terbinafine and its mechanism of action

Answer 44

an allylamine - a synthetic antifungal agent
it is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues

Mechanism of action
As with the other allylamines, terbinafine inhibits ergosterol biosynthesis via inhibition of squalene epoxidase. This enzyme is part of the fungal sterol synthesis pathway that creates the sterols needed for the fungal cell membrane

Question 45

TYPES OF SYSTEMIC MYCOSES

Answer 45

I Cryptococcus neoformans
II Pneumocystis carinii
III Blastomycosis
IV Histoplasmosis
V Aspergillosis

Question 46

I Cryptococcus neoformans (reproduction and pathology)

Answer 46

A serious pathogenic yeast
This yeast can also reproduce sexually; the sexual form of the yeast is called Filobasidiella neoformans.
It appears as an oval yeast 5-6 µm in diameter, forms buds with a thin neck, and is surrounded by a thick capsule. It does not produce pseudohyphae and chlamydospores. The capsule enables the yeast to resist phagocytic engulfment.

Question 47

I Cryptococcus neoformans

infections and where they are found

Answer 47

Cryptococcus infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird faeces.

It is typically associated with pigeon and chicken droppings and soil contaminated with these droppings.

Cryptococcus, found in soil, actively grows in the bird faeces but does not grow in the bird itself.

Usually the infection does not proceed beyond this pulmonary stage

Question 48

I Cryptococcus neoformans

in the immunosuppressed host and outbreaks

Answer 48

it may spread through the blood to the meninges and other body areas, often causing cryptococcal meningoencephalitis (a very severe and usually fatal infection). Any disease by this yeast is usually called cryptococcosis.

Cutaneous and visceral infections are also found.

Although exposure to the organism is probably common, large outbreaks are rare, indicating that an immunosuppressed host is usually required for the development of severe disease.

Extrapulmonary cryptococcosis, in conjunction with a positive HIV antibody test, is a good indicator disease for AIDS.

Question 49

The C. neoformans infectious cycle

Answer 49

C. neoformans resides in the environment and has been found associated primarily with pigeon droppings.

It is thought that infection of humans generally occurs when basidiospores produced by C. neoformans in nature are inhaled into the lungs.
Inhaled spores are deposited into the alveoli and germinate to establish a dormant infection or disseminate to the central nervous system.

Once dissemination has occurred, viable cells can be cultured from the cerebrospinal fluid of affected individuals.

Question 50

II Pneumocystis carinii (morphology)

Answer 50

based on its appearance and sensitivity to antiprotozoan drugs, was long thought to be a protozoan, analysis of its ribosomes and cell wall show it to be more closely related to the fungi than the protozoans.

Question 51

II P carinii (transmission and what disease it causes)

Answer 51

P. carinii is thought to be transmitted from person to person by the respiratory route and is almost always asymptomatic.

However, in persons with highly depressed immune responses, such as people with leukemias or infected with the Human Immunodeficiency Virus (HIV), P. carinii can cause an often lethal pneumonia called PCP (Pneumocystis carinii pneumonia).

Question 52

III Blastomycosis

Answer 52

Disease caused by the dimorphic fungus Blastomyces dermatitidis (dimorphic = having two distinct forms, as in some fungal pathogens of humans, which are yeast-like in the host, but mycelial in culture)

Question 53

endemics of Blastomycosis and its infection

Answer 53

• Endemic in the southeastern and south central states of North America
• Outbreaks have been associated with occupational or recreational activities around streams or rivers with high content of moist soil enriched with organic debris and/or rotting wood.
• Infection is acquired via inhalation of the conidia, which transform into the yeast form once in the lungs.
• After 30 to 45 days an acute pulmonary disease indistinguishable from a bacterial pneumonia may occur.
• However, at least 50% of primary infections are asymptomatic

Question 54

IV Histoplasmosis

Answer 54

Condition caused by infection with the dimorphic endemic fungus Histoplasma capsulatum

The most common cause of fungal respiratory infections in the world. The majority of acute cases of infection with this fungus follow a sub-clinical and benign course in normal hosts.

However, a disseminated and potentially fatal picture is seen among immunosuppressed individuals, children <2 years old, the elderly and people exposed to a very large inoculum.

Since the advent of the HIV epidemic, histoplasmosis has re-emerged to become one of the most frequent opportunistic diseases

Question 55

Histoplasmosis infection

Answer 55

The infection is acquired through inhalation of Histoplasma capsulatum microconidia. The lungs are thus the most frequently affected site and chronic pulmonary disease may occur. This clinical picture is frequently associated with pre-existing chronic lung diseases such as emphysema and occurs most frequently in elderly men. All stages of this disease may mimic tuberculosis

Question 56

environment and forms of Histoplasmosis

Answer 56

The mold or mycelial form exists in the soil, where it absorbs nutrients from dead organic matter and produces infectious spores. When these spores are inhaled and encounter the warm moist environment of the lungs, they undergo a transformation to the yeast or parasitic form

Question 57

V Aspergillosis

Answer 57

Refers to the broad range of disease states whose etiologic agents are members of the genus Aspergillus

Aspergillus spp. are ubiquitous organisms, progressively associated with a growing spectrum of infections in immunocompromised hosts.

Aspergillus fumigatus is responsible for over 90% of cases of invasive aspergillosis

Question 58

The three most prevalent diseases cause by Aspergillosis

Answer 58

allergic bronchopulmonary aspergillosis,

pulmonary aspergilloma and

invasive aspergillosis (gives rise to a systemic spread)

Question 59

Allergic bronchopulmonary Aspergillosis

Answer 59

produces an allergy to the spores of Aspergillus molds
common in asthmatics (up to 20% of asthmatics might get this at some time during their lives).
also common in cystic fibrosis patients, as they reach adolescence and adulthood.

Question 60

symptoms of Allergic bronchopulmonary Aspergillosis

Answer 60

symptoms are similar to those of asthma: intermittent episodes of feeling unwell, coughing and wheezing. Some patients cough up brown-coloured plugs of mucus. The diagnosis can be made by X-ray or by sputum, skin and blood tests. In the long term can lead to permanent lung damage (fibrosis) if untreated

Question 61

Aspergilloma

Answer 61

• disease in which Aspergillus grows within a cavity of the lung, which was previously damaged during an illness such as tuberculosis
• any lung disease which causes cavities can leave a person open to developing an aspergilloma. The spores penetrate the cavity and germinate, forming a fungal ball within the cavity. Illness is caused by secretion of toxins/other products (elastases, proteases)

Question 62

symptoms of Aspergilloma

Answer 62

The person affected may have no symptoms (especially early on). Weight changes, chronic cough, brain fog, and feeling rundown are common symptoms later. Coughing of blood (hemoptysis) can occur in up to 50-80% of affected people. The diagnosis is made by X-rays, scans of lungs and blood tests.

Question 63

Invasive Aspergillosis

Answer 63

often fatal.

no good diagnostic test.

often treatment has to be started when the condition is only suspected.

usually clinically diagnosed in a person with low defences such as bone marrow transplant, low white cells after cancer treatment, AIDS or major burns.
There is also a rare inherited condition that gives people low immunity (chronic granulomatous disease) which puts affected people at moderate risk.

Question 64

symptoms of Aspergillosis and its diagnosis

Answer 64

People with invasive Aspergillosis usually have a fever and symptoms from the lungs (cough, chest pain or discomfort or breathlessness) which do not respond to standard antibiotics. X-rays and scans are usually abnormal and help to localize the disease

Bronchoscopy (inspection of the inside of the lung with a small tube inserted via the nose) is often used to help to confirm the diagnosis

Question 65

Treatment and Control of Systemic Pathogenic Fungi

Answer 65

Effective chemotherapy against systemic fungal infections is very difficult

One of the most effective antibiotics is amphotericin B, a polyene (binds to membrane sterols & affects the integrity of the fungal cell membrane)

However, this antibiotic can give rise to serious side effects e.g. kidney toxicity

Exposure to fungi can rarely be eliminated except using air filtration in restricted local environments

Question 66

FUNGAL PATHOGENICITY

Virulence factors that promote fungal colonization

Answer 66

LOOK AT L14 S45

IMPORTANT

Question 67

FUNGAL PATHOGENICITY

Virulence factors that damage the host

Answer 67

LOOK AT L14 S46

IMPORTANT