Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Medical & General Microbiology > Fungal Pathogens III > Flashcards

Fungal Pathogens III Flashcards

(56 cards)

Start Studying
1
Q

Fungal resistance is not as big a problem as antibiotic resistance because

A

Fungi do not have horizontal gene transfer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Types of antifungal agents

A
  1. Membrane disrupting agents (polyenes)
  2. Ergosterol synthesis inhibitors (azoles, allylamines)
  3. DNA synthesis inhibitors (flucytosine)
  4. Glucan synthesis inhibitors (echinocandins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why are there so few antifungals?

A
  1. Fungi are eukaryotes so closely related to our cells

2. Antifungals are very difficult to get into fungi (cell wall and efflux pumps)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Polyenes

A

Membrane disrupting agents
Associate with ergosterol to form pores
Leak cations Na and Ca
Nystatin and Amphotericin B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Ergosterol is the fungal equivalent of

A

Cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Polyenes can be toxic due to them binding to

A

Human cholesterol

Ergosterol and cholesterol structures very similar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Nystatin is used for

A

Superficial infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Amphotericin B is used for

A

Systemic infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Amphotericin B problems

A

IV use only

Nephrotoxicity (kidneys)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Polyenes have

A

A wide spectrum

Candida, cryptococcus, aspergillus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Azoles are the

A

Largest group of antifungals (5)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Azole refers to the

A

5 membered heterocyclic ring (Nitrogens)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Imidazole has

A

2 N, rarely used, toxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Triazole has

A

3 N, commonly used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Azoles inhibit

A

Ergosterol synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Azoles block the

A

14 alpha sterol demethylase (enzyme that demethylates lanosterol)
Blocks haem iron in the enzyme

Alters membrane fluidity (rigid)as alpha sterols build up

FUNGISTATIC - blocks growth but does not kill them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Azoles stop the demethylation of

A

Lanosterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

14 alpha sterol demethylase demethylates

A

Lanosterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Azoles have a

A

Broad spectrum

Except - fluconazole, does not work on aspergillus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Azoles are mainly

A

Fungistatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Azoles problems

A
  1. Drug interactions:
    - target enzyme related to cytochrome P450
    - can block human P450 in the liver so affect drug metabolism of other drugs
  2. Resistance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Allylamines inhibit

A

Ergosterol biosynthesis - squalene epoxidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Allylamines cause cells to

Study These Flashcards
A

Accumulate squalene which is toxic

24
Q

Accumulation of squalene is

25
Allylamines are most effective against
Dermatophytes limited use in candida, aspergillus and cryptococcus
26
5 flucytosine (5FC) is a
Synthetic analogue of cytosine
27
5FC enters cells through
Cytosine permease (enzyme in cell wall)
28
5FC is converted by cytosine deaminase to
5 Fluoroucil (5FU)
29
5FC inhibits
Protein and DNA synthesis
30
5FU gets incorporated into
mRNA | The ribosome cannot read it
31
5FC only works against
Yeasts Candida and cryptococcus (filamentous fungi lack cytosine permease and cytosine deaminase)
32
5FC problems
Resistance is very common | Not used as a single agent and never in candida
33
Echinocandins are
Semi synthetic (developed in 2000's)
34
Echinocandins inhibit
Beta 1,3 glucan synthase | essential component of cell wall
35
Echinocandins can be either fungistatic or fungicidal
Fungicidal in candida Fungistatic in aspergillus Not effective in cryptococcus
36
Echinocandins good things
No problem of cross resistance | Low toxicity
37
Echinocandins problems
Not effective against cryptococcus IV use only Expensive
38
Treating superficial infections
Dermatophytes - allylamines | Candida - Azoles
39
Treating systemic infections
Azoles Amphotericin B (IV) Echinocandins (IV)
40
Mechanisms of resistance
1. Primary/Natural | 2. Secondary/Aquired
41
Primary/Natural resistance
Intrinsic resistance linked to species or strain (Allylamines not effective against candida) (Fluconazole intrinsically not effective against cryptococcus)
42
Secondary/Aquired resistance
Susceptible strain becomes resistant | Mutation and selection
43
Resistance to Amphotericin B is
Rare
44
Mechanism of Amp B resistance
1. Reduced/alteration of ergosterol content 2. Alteration of sterol/phospholipid balance 3. Increased catalase activity (combat oxidative stress associated with amphotericin exposure)
45
Resistance to Flucytosine
Primary ( ALL filamentous fungi) (10% of candida) Secondary (monotherapy, 30% candida resistant after treatment)
46
Flucytosine mechanism of resistance
1. Loss of permease activity 2. Loss of cytosine deaminase activity 3. Decrease in the activity of uracil phosphoribosyl-transferase Partial resistance to 5FU is achieved through blocking action in mRNA Mutations
47
Resistance to Echinocandins
Primary - cryptococcus | Secondary - rare
48
Echinocandin mechanism of resistance
Point mutations in beta 1,3 glucan synthase | Upregulated chitin synthesis
49
Resistance to azoles
Primary - aspergillus, cryptococcus | Secondary - candida, common in HIV
50
Azole resistance mechanism
1. Reduced accumulation of azole (overexpression of efflux pumps) 2. Alteration of target enzyme (point mutations decrease affinity of azole) 3. Upregulate ERG11 (need more drug to compete) 4. Alterations in sterol synthesis - blocking methylation (causes dual resistance to azoles and polyenes)
51
ERG11
Ergosterol biosynthesis
52
Mechanisms of resistance can be
Cumulative/additive
53
The 4 classes of antifungal agents
1. Azoles 2. Polyenes 3. Echinocandins 4. Flucytosine
54
Limitations of antifungals
Interactions Toxicity Resistance Cost and availability
55
Resistance is common with
Flucytosine
56
Resistance is rare with
Azoles, polyenes, echinocandins

Medical & General Microbiology (24 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions