Mycology second half Questions With Complete Solutions
Aspergillus hyphae
Hyphal cells have galactomannan and galactosaminogalactan
(GAG) in their outer cell wall
GAG is also secreted into the extracellular environment.
GAG plays a crucial role in adherence of hyphae to surfaces and
host cells
GAG can help mask immune detection via beta-glucan masking
Secreted GAG induces apoptosis of neutrophils
Summary of Aspergillus immune evasion strategies
Conidia have hydrophobins (rodlets) on their surface that shield
β-glucan recognition
As conidia swell, β-glucan becomes exposed, but melanin helps
inhibit phagocytosis ("LAP") by macrophages, and neutralizes
host ROS
Hyphal cells produce GAG and gliotoxin which can induce
apoptosis in neutrophils and macrophages, GAG can also mask
β-glucan
Aspergillus biofilms
Aspergillus hyphae can develop into a dense mycelium that
secretes an extracellular matrix (ECM) to form a biofilm
Hyphal-secreted GAG is a key part of the ECM that helps with
adherence.
Biofilms are often associated with aspergillomas
Biofilms are highly resistant to antifungal drug treatment
,Aspergillus diagnosis
Chest x-rays, and microscopy from tissue biopsies looking for
Aspergillus morphologies (conidia, hyphae, conidiophores, etc)
using silver staining
Rapid immunoassays for Aspergillus detect of galactomannan
antigen in patient serum by enzyme immunoassay (EIA)
Antifungal drugs
Fungi are evolutionarily very similar to humans and plants!
(especially compared to bacteria)
Antifungals explot some of the key differences between fungi
and humans:
Polyenes, azoles, and allylamines target the fungal cell
membrane, echinocandins target the fungal cell wall.
Fungistatic vs fungicidal drugs
Fungistatic: antifungals arrest fungal growth without killing the
fungus
Fungicidal: antifungals result in fungal killing
Polyenes
First class of antifungal drugs identified
Bind to fungal ergosterol (sterol of the fungal cell membrane,
distinct from human cholesterol), and punch holes in the
membrane causing pore formation and ion (K+ and Na+)
leakage resulting in fungal cell death (fungicidal)
Polyenes are notable for very severe side effects (kidney, liver
damage) due to similarities between human cholesterol and
fungal ergosterol
,Common polyenes: Amphotericin B (treatment of invasive
aspergillosis, blastomycosis, candidiasis, coccidioidomycosis,
and cryptococcosis by IV), Nystatin (used topically or orally for
skin, vaginal, mouth, and esophageal Candida infections).
Azoles
Azoles are the most widely-used class of antifungals, exhibit
species-specific fungicidal or fungistatic activity (static against
Candida infections)
Inhibit ergosterol biosynthesis (conversion of lanosterol to
ergosterol) by inhibiting Erg11 (aka Cyp51), leading to the
accumulation of a toxic sterol intermediate produced by Erg3,
which causes damage to the cell membrane, increasing its
permeability.
Azoles continued how are the subdivided
Azoles are subdivided into imidazole vs triazoles based on
differences in nitrogen in the azole ring
Most imidazole are topical (ie miconazole), triazoles are newer
with better safety profiles, and are usually used systemically IV
or oral (ie fluconazole, itraconazole, voriconazole), some side
effects.
Azoles are commonly used for systemic Candida, Aspergillus,
Cryptococcus, dimorphic fungal infections, mucosal yeast
infections, dermatophyte infections.
Allylamines
Allylamines inhibit an earlier step in ergosterol biosynthesis
compared to Azoles (squalene to lanosterol), example:
, terbinafine
Mainly used topically (side effects when used systemically) to
treat dermatophytes (Athlete's foot, ringworm etc)
Echinocandins
Echinocandins inhibit the biosynthesis of glucan in the fungal
cell wall by inhibiting beta-glucan synthase enzyme Fks1/Fks2
newest class of antifungal (since 1990s) with fewest side
effects/best safety profile.
Echinocandins exhibit species-specific fungicidal or fungistatic
activity (static against Aspergillus infections)
Examples: caspofungin, micafungin, anidulafungi...
Used primarily for anole-resistant systemic Candida infections,
ineffective for treatment of Cryptococcus, dimorphic pathogen
infections, used by IV
Flucytosine
Flucytosine (aka 5-FC) is a pyrimidine analog, undergoes
several modifications, and ultimately acts by inhibiting DNA
synthesis and RNA biosynthesis (and thus blocks protein
synthesis)
Used in combination with amphotericin B for treatment of
invasive Candida and Cryptococcus infections - used on its own,
resistance rates are very high
Novel antifungal drugs
Increasing prevalence of fungal infections and increasing rates
of antifungal drug resistance has generated demand for new
antifungal drugs with novel mechanisms of action
Aspergillus hyphae
Hyphal cells have galactomannan and galactosaminogalactan
(GAG) in their outer cell wall
GAG is also secreted into the extracellular environment.
GAG plays a crucial role in adherence of hyphae to surfaces and
host cells
GAG can help mask immune detection via beta-glucan masking
Secreted GAG induces apoptosis of neutrophils
Summary of Aspergillus immune evasion strategies
Conidia have hydrophobins (rodlets) on their surface that shield
β-glucan recognition
As conidia swell, β-glucan becomes exposed, but melanin helps
inhibit phagocytosis ("LAP") by macrophages, and neutralizes
host ROS
Hyphal cells produce GAG and gliotoxin which can induce
apoptosis in neutrophils and macrophages, GAG can also mask
β-glucan
Aspergillus biofilms
Aspergillus hyphae can develop into a dense mycelium that
secretes an extracellular matrix (ECM) to form a biofilm
Hyphal-secreted GAG is a key part of the ECM that helps with
adherence.
Biofilms are often associated with aspergillomas
Biofilms are highly resistant to antifungal drug treatment
,Aspergillus diagnosis
Chest x-rays, and microscopy from tissue biopsies looking for
Aspergillus morphologies (conidia, hyphae, conidiophores, etc)
using silver staining
Rapid immunoassays for Aspergillus detect of galactomannan
antigen in patient serum by enzyme immunoassay (EIA)
Antifungal drugs
Fungi are evolutionarily very similar to humans and plants!
(especially compared to bacteria)
Antifungals explot some of the key differences between fungi
and humans:
Polyenes, azoles, and allylamines target the fungal cell
membrane, echinocandins target the fungal cell wall.
Fungistatic vs fungicidal drugs
Fungistatic: antifungals arrest fungal growth without killing the
fungus
Fungicidal: antifungals result in fungal killing
Polyenes
First class of antifungal drugs identified
Bind to fungal ergosterol (sterol of the fungal cell membrane,
distinct from human cholesterol), and punch holes in the
membrane causing pore formation and ion (K+ and Na+)
leakage resulting in fungal cell death (fungicidal)
Polyenes are notable for very severe side effects (kidney, liver
damage) due to similarities between human cholesterol and
fungal ergosterol
,Common polyenes: Amphotericin B (treatment of invasive
aspergillosis, blastomycosis, candidiasis, coccidioidomycosis,
and cryptococcosis by IV), Nystatin (used topically or orally for
skin, vaginal, mouth, and esophageal Candida infections).
Azoles
Azoles are the most widely-used class of antifungals, exhibit
species-specific fungicidal or fungistatic activity (static against
Candida infections)
Inhibit ergosterol biosynthesis (conversion of lanosterol to
ergosterol) by inhibiting Erg11 (aka Cyp51), leading to the
accumulation of a toxic sterol intermediate produced by Erg3,
which causes damage to the cell membrane, increasing its
permeability.
Azoles continued how are the subdivided
Azoles are subdivided into imidazole vs triazoles based on
differences in nitrogen in the azole ring
Most imidazole are topical (ie miconazole), triazoles are newer
with better safety profiles, and are usually used systemically IV
or oral (ie fluconazole, itraconazole, voriconazole), some side
effects.
Azoles are commonly used for systemic Candida, Aspergillus,
Cryptococcus, dimorphic fungal infections, mucosal yeast
infections, dermatophyte infections.
Allylamines
Allylamines inhibit an earlier step in ergosterol biosynthesis
compared to Azoles (squalene to lanosterol), example:
, terbinafine
Mainly used topically (side effects when used systemically) to
treat dermatophytes (Athlete's foot, ringworm etc)
Echinocandins
Echinocandins inhibit the biosynthesis of glucan in the fungal
cell wall by inhibiting beta-glucan synthase enzyme Fks1/Fks2
newest class of antifungal (since 1990s) with fewest side
effects/best safety profile.
Echinocandins exhibit species-specific fungicidal or fungistatic
activity (static against Aspergillus infections)
Examples: caspofungin, micafungin, anidulafungi...
Used primarily for anole-resistant systemic Candida infections,
ineffective for treatment of Cryptococcus, dimorphic pathogen
infections, used by IV
Flucytosine
Flucytosine (aka 5-FC) is a pyrimidine analog, undergoes
several modifications, and ultimately acts by inhibiting DNA
synthesis and RNA biosynthesis (and thus blocks protein
synthesis)
Used in combination with amphotericin B for treatment of
invasive Candida and Cryptococcus infections - used on its own,
resistance rates are very high
Novel antifungal drugs
Increasing prevalence of fungal infections and increasing rates
of antifungal drug resistance has generated demand for new
antifungal drugs with novel mechanisms of action
