INF1 - E. FUNGI AND ANTIFUNGALS-COVERED Flashcards
1
Q
what type of cells are fungi cells and how are they different
A
- eukaryotic cells
- haploid: single set of chromosomes
- cell wall is rigid and made of chitin, mannan, glucan
- cytoplasmic membrane contains ergosterol
2
Q
what are the 3 classes of fungi
A
- moulds
- yeasts
- mushrooms
3
Q
explain what hypae are
A
- networks of filaments which form in the environment
- can spread for long distances
- can grow in our body as a from of a fungal infection
4
Q
what 2 classes exist as multicellular (have hyphae)
A
moulds
mushrooms
5
Q
what class exists as unicellular organisms
A
yeasts
live naturally in environment but can cause infection in our body
6
Q
explain dimorphic behaviour
A
- when fungi convert from hyphae to yeast forms and vice versa (ie: hyphal form - produces spores - inhale - germinate - yeast form in body)
- dependent on temperature
- pathogenic dimorphic fungi grow as one form in outside environment and a different form in body of a host
7
Q
explain sporulation
A
- fungi form spores
- allows fungi to spread, maintain genetic diversity and survive adverse conditions
- spores are airborne
8
Q
how do fungal infections arise (aka mycoses)
A
- overgrowth of normal flora (yeasts - oral and vaginal thrush and dermatophytes on skin ie, nails - athletes foot and ringworm)
- inhalation of fungal spores
- traumatic implantation of fungal spores from a sharp nail and hence germination and growth in tissues
9
Q
what are fungal pathogenicity factors
A
- adhesion to host cells (proteins etc) - TROPISM
- capsules to prevent phagocytosis
- enzymes to facilitate tissue invasion and suppress immune system
- don’t produce/release exotoxins or endotoxins
10
Q
what are superficial infections
A
- on surface layers
- hair shaft, dead layer of skin
- piedras - pityriasis versicolor
- skin blemishes/weakened hair shafts
- yeast or fungi
11
Q
what are cutaneous infections
A
- in deeper layers
- epidermis, nails
- tineas - athletes foot and ringworm
- fungi
12
Q
what are subcutaneous infections
A
- in muscle layers - spores implanted in deeper layers
- dermis, subcutis
- mycetoma, chromoblastomycosis, sporotrichosis
- deep, tissue damaging (traumatic implantation)
- fungi
13
Q
what are systemic infections
A
- in bloodstream (lungs, internal organs)
- blastomycosis, cryptococcal meningitis, histoplasmosis, coccidioidomycosis
- inhalation of spores
- grow as hyphae, become more like yeast, get into blood
14
Q
what are opportunistic infections
A
- mucosal tissues, internal organs, systemic
- live in one environment but can exploit an opportunity and cause a more serious infection
- candidosis, aspergillosis - environmental infection, Farmers lung - hyphae to spores to hyphae
15
Q
what causes poisoning/allergies
A
fungal toxins (mycotoxins)
ie - ergot in wheat, peanuts, mushrooms
16
Q
examples of hyphal forms to yeast-like forms
A
Cryptococcosis - causes fungal meningitis (fungi in grown bird/bat droppings, release spores, inhaled)
Coccidioidomycosis - skin, meningitis, bone
17
Q
example of yeast-like form to hyphal form
A
Candida albicans - part off microbiome, can cause thrush and maybe systemic infections)
18
Q
what are superficial mycoses
A
- harmless, minimal destructive damage
- white pier: infection of hair shaft, white nodules cause thinning and breakage of hair
- pityriasis versicolor: red/brown blemishes
- topical treatment:
- selenium-based shampoo
- ketocanazole body wash
19
Q
what are cutaneous mycoses
A
- dermatophyte fungi digest keratin found in hair, nails, skin
- tinea capitis: infection of hair and scalp
- tinea corporis: infection of trunk, arms, legs
- tinea pedis: athletes foot
- tinea cruris: genital itch
- tinea unguium: nail infection
- contagious
- topical agents or systemic therapy for extensive infection
20
Q
what are subcutaneous mycoses
A
- fungi introduced by trauma, wounds, splinters, thorns
- amputations/surgical extension?
- chromoblastomycosis
- mycetoma
21
Q
what are systemic mycoses
A
- often opportunistic pathogens ie - candida
- infection by spore inhalation ie - cryptococcosis, aspergillosis
- spread from mucosal infections ie - candidiosis
- often caused by dimorphic behaviour
- aggressive therapy
22
Q
what are opportunistic infections
A
- Candida albicans
- part of mucosal and cutaneous microflora, live on moist regions of body
- oral thrush (antibiotic use/immunocompromised state)
- vaginal thrush (change in vaginal pH)
- candidiosis common in diabetes (poor blood circulation), cancer, HIV, burns patients, post surgery infection
- systemic infection
- dimorphic (yeast to hyphae) - Candida auris
- superbug - major cause of hospital-acquired infections - Aspergillus fumigatus
- found in wet soil/damp surfaces
- spore inhalation, drowns as hyphal form in lung tissue
- release toxins like phospolipases, haemolysins - damage lungs, facilitate spread
- pulmonary aspergillosis: farmers lung - Cryptococcus neoformans (Crytpococcosis)
- found in soil contaminated with bird dropping
- inhalation of spores
- immunocompromised patients and cause for meningitis in AIDS patients
- surrounded by capsules - infection and immune invasion
- phagocytoses by macrophages, surviving and multiplying within macrophage and trafficked around body
23
Q
what does a fungal cell consist of
A
nucleus
mitotic spindle
endoplasmic membrane (synthesis of ergosterol)
membrane (ergosterol)
cell wall
24
Q
why are there fewer systemic fungal treatments
A
- less common than bacterial infections
- fungal cells are eukaryotic - difficult to make compounds specific and non-toxic to host cells
- poor solubility, absorption, stability
25
what do polyenes target and how do they act
- bind to ergosterol in cell membrane
- therefore preference for fungal cells rather than human cells
- dosing important so cholesterol not targeted
- fungicidal
- causes leakage of cell contents
- renal toxicity is a side effect
- IV injection: lipid complex or liposome delivery
- drug molecules orient themselves parallel to side chains of CM to form cylindrical channel/pores, cell death
- Amphotericin B and Nystatin
26
what do azoles target and how do they act
- target sterol synthesis
- inhibit precursor stage of ergosterol biosynthesis
- bind to fungal P450 enzyme (haem group) which makes ergosterol (14 alpha-sterol demethylase) so membrane stability disrupted
- fungistatic: stop cell growing but still remains live
- reaction dependent on cytochrome P450
- can interfere with mammalian sterol metabolism (testosterone)
- Ketoconazole, Fluconazole, Itraconazole (imidazoles, triazoles)
27
what do nucleoside derivatives target and how do they act
- block DNA/RNA synthesis
- relies on selective uptake (ie - mechanisms that don't exist in our cells)/metabolic activation in fungal cell
- active uptake, converted to 5-flurouracil (fungal selectivity)
- further converted to 5-fluorouridylic acid monophosphate (FUMP - inhibits RNA synthesis) or 5-fluorodeoxyuridine monophosphate (inhibits DNA synthesis)
- Flucytosine
28
what do echinocandins target and how do they act
- block cell wall synthesis by blocking beta 1-3 glucan polymer synthesis
- cyclic lipopeptides that non-competitively inhibit 1,3-beta-D glucan synthase
- this integral membrane exports glucan polymer
- Caspafungin
29
what do grisans target and how do they act
- inhibit microtubule functions by interfering with tubulin and therefore mitosis and cell division
- may affect cell wall synthesis by inhibiting chitin synthesis
- Griseofulvin
30
what do allylamines target and how do they act
- target squalene epoxidase (enzymes in ergosterol synthesis)
- Naftifine, Terbinafine
31
what do morpholines target and how do they act
- target ergosterol synthesis by inhibiting reductase and isomerase
- Amorolfine
32
why does resistance to polyenes occur
- usually primary resistance (naturally)
- lower production of sterols
- altered sterols which bind drug with lower affinity
- reorientation/masking of existing ergosterol to limit polyenes binding
33
why does resistance to nucleosides (pyrimidine analogues) occur
- usually secondary resistance
- decreased uptake
- loss of enzymatic activity responsible for conversion to FUMP by loss of cytosine permease/deaminase
34
why does resistance to azoles occur
- usually secondary resistance
- increase content of target enzymes by gene amplification/upregulation of encoding gene
- mutations in 14-alpha lanosterol demethylase enzyme
- active efflux (ABC transporters which use energy to pump out drug molecules)
- resistance has risen due to use in HIV patients with mucosal fungal infections
35
why does resistance to enchinocandins occur
- mutations in glucan synthase target (acquired/secondary resistance)
36
other resistance mechanisms
- formation of biofilms
- anti fungal drug has poor penetration in biofilm and efflux pumps in fungal biofilms are unregulated
