Micro 01 - Fungi Overview

Front 1

Key differences between Animals and Fungi?

Back 1

-Ergosterol in membrane instead of Cholesterol
-have a Cell Wall made of chitin, glucan, and mannan

Front 2

Type of nutritional organism Fungi are?

Back 2

Heterotrophs = cannot synthesize their own nutrients, but assimilate nutrients from surroundings

Front 3

How is being a heterotroph imporant in the way Fungi cause disease in humans?

Back 3

Fungi secrete enzymes that digest the substrate..aka our tissue (amylase, lipase, cellulase, proteinase)

Front 4

2 morphological forms of fungi?

Back 4

Yeasts

Filaments

Front 5

Filaments are long, hollow structures filled with __1__ and often divided by __2__

Back 5

1. cytoplasm
2. cross-walls

Front 6

Filaments are larger than __1__, they can break apart and each fragment can __2__. The filament form allows for __3__

Back 6

1. macrophages
2. start a new colony
3. tissue penetration

Front 7

Yeasts are __1__-cellular and divide by __2__

Back 7

1. uni
2. fission (budding)

Front 8

Host defense against filaments:

Host defense against yeast:

Back 8

Oxidative burst


Phagocytosis

Front 9

Pathogenic Fungi:
-some have the ability to grow at __1__ degrees.
-Some have a __2__ which protects them from immune system
-__3__ allows them deep penetration of the lung where systemic infection can start

Back 9

1. 37' C
2. polysaccharide capsule
3. small spore size

Front 10

Interaction with _______ may predispose fungi to be parasites of higher animals

Back 10

soil amoebae

Front 11

4 major groups of fungi

Back 11

Ascomycetes
Basidiomycetes
Zygomycetes
Imperfect fungi

Front 12

The four groups are differentiated based on _________

Back 12

their spore types

Front 13

List some examples of Asexual spores

Back 13

Arthrospore
Chlamydospore
Fusarium conidia
Alternaria conidia
Neurospora conidia

Front 14

Asexual spores have these characteristics

Back 14

-vary in size from a few microns to hundreds of microns
-often very Hydrophobic
-some have mucilage

Front 15

What stage of fungal life cycle is most relevant to allergy sufferers?

Back 15

Spores are often allergenic
-dead spores maintain allergenicity

Front 16

Most numerous spores in the air we breath?

Back 16

Conidia, but also smut spores and ascospores

Front 17

Type of Hypersensitivity caused by spores?

Back 17

Type I: spore binds to IgE on Mast cells

Front 18

4 most common environmental fungi

Back 18

Aspergillus
Alternaria
Cladosporium
Penicillium

*their spores are common indoors and outdoors*

Front 19

Spores are common after _______ events

Spores are not common in these environments: _____

Back 19

rain

desert/arid

Front 20

Some ______ infections can be related to fungal presence

Back 20

sinus

*Eosinophilic Fungal Rhinosinusitis
*difficult to tell if fungi are growing in sinus or incidental

Front 21

Where are typical locations of fungi indoors?

Back 21

Moisture places
-shower
-water ducts
-furnace filters
-house plants

Front 22

Household item that can kill fungi

Back 22

bleach

Front 23

Most common fungal toxins and most significant public health risk associated with fungi

Back 23

Mycotoxins in grain

Front 24

-Estimated # of different mycotoxins: __1__
-Toxin also common in __2__
-__3__ poisoning is much less common than mycotoxin exposure

Back 24

1. 300-400
2. nuts
3. mushroom

Front 25

Aflatoxin is from grains and nuts infected by ________

Back 25

Aspergillus

Front 26

Explain how Aflatoxin is activated

Back 26

It is metabolized to its active form in the Liver

Front 27

What can complicate Aflatoxin ingestion?

Back 27

HBV + Aflatoxin exposure have higher incidences of LIVER CANCER

Front 28

Alkaloid mycotoxins include these 3

Back 28

1. Clavicepes infected rye -> Lysergic Acid (LSD)
2. St. Anthony's fire = hallucinations, cramps
3. Neurotoxins in infected grains

Front 29

Fumonisin mycotoxins come from __1__ infected __2__
-It is associated with __3__ CA.
-causes disease in __4__

Back 29

1. Fusarium
2. Wheat
3. Esophageal
4. farm animals

Front 30

Example of a Fumonisin mycotoxin

Back 30

Vomitoxin

*produced by Fusarium

Front 31

Fungus that causes "sick building syndrome"

Back 31

Stachybotrys Chartrum

Front 32

Stachybotrys Chartum mycotoxins

Concentration of infected material that can contain a lethal dose

Back 32

Trichothecenes
Satratoxin F, G, and H

100-1000 cm'2

Front 33

People in contaminated buildings have elevated titers of antibodies to:
-S. Chartum: __1__
-Satratoxin: __2__

Back 33

1. IgA, IgM, IgE

2. IgG

*Stachybotrys is relatively uncommon compared to enviromental Alternarium, Cladosporium, Aspergillus

Front 34

Gliotoxin is produced by these 2 fungi

Back 34

Aspergillus
Gliocladium

Front 35

3 properties of Gliotoxin

Gliotoxin mechanism?

Back 35

1. highly toxic
2. immunomodulatory
3. stimulates apoptosis

Mechanism: inhibits nuclear factor kappa B

Front 36

Are most cases of Mushroom poisoning lethal or non-lethal?

Back 36

Non-lethal

Front 37

What is the most common symptom of Mushroom poisoning?

Back 37

Vomiting

Front 38

Amanita toxins are __1__ polypeptides which inhibit __2__

Back 38

1. cyclic
2. RNA Polymerase

Front 39

Amanita toxins can lead to death within __1__ days without a __2__ transplant

Back 39

1. 6
2. liver

Front 40

Ibotenic Acid toxin is produced by __1__ and causes these symptoms: __2__

Back 40

1. Amanita muscaria
2. nausea, vomiting, confusion, visual distortion

Front 41

Psilocybin causes these clinical effects

Back 41

Hallucinations or Perceptual distortions

Front 42

Why are Anti-fungal therepies limited?

Back 42

Fungi are closer to animals than bacteria are
-many drugs that kill fungi are bad for people as well

Front 43

Most anti-fungal therapies depend on the presence of ________ in the fungal membrane

Back 43

Ergosterol

Front 44

Fungi use __1__ in their membranes

Animals use __2__ in their membranes

Back 44

1. Ergosterol

2. Cholesterol

Front 45

List the pathway to Ergosterol synthesis

Back 45

Squalene --> Lanosterol --> Ergosterol

Front 46

2 antifungal classes that target Squalene Epoxidase

Back 46

Thiocarbamates
Allylamines

Front 47

Thiocarbamates and Allylamines are effective against __1__ but less so against __2__

Back 47

1. Dermatophytes
2. yeast

Front 48

Squalene accumulation can be ______ to the fungi

Back 48

toxic

Front 49

List 4 Allylamines

Back 49

Terbinafine
Naftifine
Amorolfine
Butenafine

*all end in FINE

Front 50

Lamisil is also known as _________

What is it effective against?

Back 50

Terbinafine

Oral or Topical
-effective against molds, dermatophytes, some candida yeasts

Front 51

What is the 1st commited step in Ergosterol synthesis?

Back 51

Squalene

Front 52

Terbinafine is marketed to __1__ because of higher frequency of __2__ infections

Back 52

1. Athletes
2. toenail/foot

Front 53

Terbinafine (lamisil):
-__1__ due to squalene accumulation.
-1/2 life is __2__ following oral administration
-take orally for __3__
-topical OTC for __4__ or _5_

Back 53

1. FUNGICIDAL
2. 4.6 hours
3. Onychomycosis (nail infection)
4. ringworm or athletes foot

Front 54

Oral Terbinafine has reduced clearance in patients with __1__ or __2__ impairment

Back 54

1. liver
2. kidney

Front 55

Terbinafine has a ______ times higher affinity for fungal squalene epoxidase than for human

Back 55

4000

Front 56

Azoles bind to _____ and inhibit __________

Back 56

P450 (14DM)

Lanosterol Demethylase
(14 alpha-demethylation of lanosterol)

*newer Azoles have a higher specificity for fungal enzyme while older azoles cross react with human P450's

Front 57

Fluconazole trade name

Back 57

Diflucan

Front 58

__________ biochemistry is markedly effected by reduction in renal fxn

Back 58

Fluconazole

Front 59

Fluconazole (Diflucan):
-half life: __1__
-effective against __2__

Back 59

1. 30 days
2. yeasts, widely used for serious fungal infections

Front 60

Fluconazole: fungistatic or fungicidal?

Back 60

Fungistatic

*need immune system to clear organisms

Front 61

Type of Fluconazole formulations available?

Back 61

Oral or IV

Front 62

Antifungal drug that penetrates into all body fluids

Back 62

Fluconazole

Front 63

Fluconazole is marketed for _________ infections

Back 63

Vulvovaginal candidiasis

Front 64

Fluconazole:
-__1__% is excreted in urine unchanged
-prophylactic in __2__

Back 64

1. 80%
2. HIV and transplant recipients

Front 65

Itraconazole formulations available

Back 65

Oral or IV

Front 66

_______ Itraconazole is unpredictable

Back 66

Oral
-best with food

Front 67

Itraconazole inhibits a broad range of fungi except __1__ and __2__

Back 67

Fusarium

Zygomycetes

Front 68

Itraconazole trade name

Back 68

Sporanox

Front 69

Property of Itraconazole

Back 69

Lipophilic = accumulates in nails and fatty tissue

Front 70

Solution or IV Itraconazole are used for some systemic infections especially in _________

Back 70

IC'ed patients

Front 71

Antifungal that is contraindicated in patients with Heart or Liver Disease

Back 71

Itraconazole

Front 72

40% of Itraconazole is excreted as _________ in urine

Back 72

inactive metabolites

Front 73

Issue with Itraconazole

Back 73

serious drug interactions

Front 74

Voriconazole trade name:

It is marketed for:

Back 74

Vfend

Aspergillosis

Front 75

Voriconazole is fungistatic to these fungi

Back 75

Candida
Aspergillus
Cryptococcus
Blastomyces
Coccidioides
Histoplasma
Fusarium
Penicillium

Front 76

Voriconazole is not effective against ________

Back 76

Zygomycetes

Front 77

Voriconazole half-life is ________

Back 77

Dose dependent, enzyme saturation

Front 78

Survival rate of 71% in patients with solid organ tranplants on __1__, compared to 58% with __2__

Back 78

1. Voriconazole
2. Amphotericin B

Front 79

Rifampicin is contraindicated with this antifungal drug

Back 79

Voriconazole

Front 80

Side effects of Voriconazole (2)

Back 80

Visual disturbances
Hepatic issues

Front 81

____% of Voriconazole is excreted as metabolites in the urine

Back 81

80%
-<2% is unchanged

Front 82

This new azole drug is broadly active but cross resistance with Itraconazole or Fluconazole.
It has a stronger inhibition of P450 target than Itraconazole

Back 82

Posaconazole (Noxafil)

Front 83

Posaconazole trade name

Back 83

Noxafil

Front 84

New azole drug with similar activity to Fluconazole and Voriconazole and Itraconazole

Back 84

Ravuconazole

Front 85

Class of Antifungals that disrupt fungal membrane by forming pores

Back 85

Polyene antibiotics (macrolides)

Front 86

Are polyene antibiotics fungistatic or fungicidal?

Back 86

Fungicidal

Front 87

2 polyene antibiotics

Back 87

1. Amphotericin B

2. Nystatin

Front 88

Nystatin was developed from ______.

There are new _____ formulations

Back 88

soil Actinomycete

Liposomal

Front 89

Topical Nystatin is used for: 1

Nystatin lozenges are used for: 2

Oral Nystatin for: 3

Back 89

1. Cutaneous candidiasis

2. Oropharyngeal candidiasis (thrush)

3. vulvovaginal candidiasis

Front 90

Is nystatin resistance common or uncommon?

What is Nystatin not useful for?

Back 90

uncommon

Systemic infections

Front 91

Nystatin is not presently useful for ________ treatment

Back 91

systemic

Front 92

Amphotericin B: fungicidal or fungistatic?

Back 92

Fungicidal

Front 93

Amphotericin B has broad range activity except against __1__ and __2__

Back 93

1. Fusarium

2. Malassezia

Front 94

Amphotericin B resistance is uncommon but can be clinically relevant in _______

Back 94

Candida

Front 95

Amphotericin B plasma half-life: _1_

Elimination half-life: _2_

Back 95

1. 24 hours

2. 15 days

Front 96

What is the first line of defense for Systemic and Opportunistic infections?

Back 96

Amphotericin B

Front 97

Serious side effects of Amphotericin include _______

Back 97

nephrotoxicity
-lipid and liposomal formulations help with this

Front 98

Most treatments with Amphotericin B require _____ administration

Back 98

IV

*oral absorption is very low

Front 99

Cerebral infections may require _______ administration of Amphotericin B

Back 99

intrathecal

Front 100

Amphotericin B is sometimes administered in combo with _______

Back 100

Flucytosine for Cryptococcal meningitis

Front 101

Dosing of Amphotericin B is based on _______

Back 101

cumulative dose
-.3 to 1.5 mg/kg over 1-4 hrs

Front 102

Amphotericin B accumulates in these 3 parts of the body

Back 102

Spleen
Liver
Lung

Front 103

Lipid formulation of Amphotericin B = 1

Liposomal formulation = 2

Back 103

1. Abelcet

2. Ambisome
-for pediatric administration

Front 104

Griseofulvin is indicated for: __1__
-half life = _2_
-cheap and is used for: _3_
-side effects: _4_
-currently clinical trials are looks at efficacy vs. __5__

Back 104

1. Dermatophytes
2. 9-24 hrs
3. tinea capitis
4. Headache, rash, confusion
5. Terbinafine

Front 105

Griseofulvin is isolated from ________

Back 105

Penicillium

Front 106

Griseofulvin disrupts _______

Back 106

mitotic spindle = inhibits mitosis

Front 107

Griseofulvin side effects

Back 107

HEADACHE
rash
confusion
photosensitivity
fatigue
nausea
peripheral neuropathy

Front 108

Echinocandins are inhibitors of ____________

Back 108

cell wall synthesis

Front 109

List 3 Echinocandins

Back 109

Caspofungin
Anidulafungin
Micafungin

*all end in FUNGIN

Front 110

Echinocandins block synthesis of _________

Derivatives of the natural product ________
Produced by _______

Back 110

1-3-beta glucan

pneumocandin Bo
Glarea Iozoyensis

Front 111

Trade name of Caspofungin

Back 111

Cancidas

Front 112

What is Caspofungin?

Back 112

An Echinocandin = inhibit glucan synthesis

Front 113

Caspofungin properties

Back 113

-poor oral bioavailability
-slow elimination (6-8 days)

Front 114

Caspofungin is prescribed for these 2 things

Back 114

Aspergillosis
Candidemia

*Glucan synthetase inhibitor

Front 115

Most serious toxin exposure is from contaminated _____

Back 115

grain

Front 116

Most common symptom of mushroom poisoning is ______

Back 116

vomiting

Front 117

Most therapies depend on targeting ________

Back 117

Ergosterol containing membranes or inhibiting sterol synthesis

Front 118

Organism in which Arthrospores are the infectious molecule

Back 118

Coccidiomycosis