Fungal Diversity & Evolution final

Explain why human‑pathogenic traits have arisen independently in multiple fungal lineages.

Convergent selection for thermotolerance, adhesion, immune evasion, and nutrient acquisition in host environments.

Discuss how fungal morphological diversity (yeast vs. hyphae vs. mushrooms) underpins ecological adaptation

Yeasts favor liquid/nutrient‑rich niches; hyphae invade solid substrates; mushrooms enable spore dispersal

Why do only ~600 of millions of fungal species associate with humans?

Human body temperature, immunity, and specific ecological constraints limit host adaptation

What fraction of fleshy mushrooms are tasty and nutritious?

4

Analyze why so few mushrooms evolved appealing flavors/nutrition

Selection favored spore dispersal traits over palatability; many produce deterrent compounds

Describe endemism of Histoplasma capsulatum and its phylogeographic species concept

Found in US Midwest, southern Ontario, parts of South America/Africa; exhibits region‑specific clades

Explain how arid‑region fungi like Coccidioides immitis have adapted to harsh environments

1. Tolerate desiccation, produce resistant arthroconidia, and grow at high soil temperatures.
   
   

Define “sclerotium” and its survival advantage

Hardened mycelial mass that endures adverse conditions and germinates when favorable

How does fungal multicellularity contrast with protist freeliving forms?

Hyphal networks allow resource translocation; fruiting bodies (reproductive structures of fungi) enable coordinated reproduction

Propose an evolutionary reason for the low proportion of edible mushrooms (~25%) being tasteless

Energy investment in flavor compounds may not benefit spore dispersal; metabolic trade‑offs

What role do mushrooms play in fungal life cycles beyond spore release

Serve as nutrient‐storage and environmental sensing structures that coordinate reproduction

Why might fungal phylogeny reveal unexpected pathogenic relatives

Fungal phylogeny can show that some fungi share a more recent common ancestor with certain pathogens than previously understood, suggesting evolutionary innovations have occurred in distinct lineages that include pathogenic traits.

Summarize the global impact of plant‑pathogenic fungi vs. human‑pathogenic fungi

~19,000 plant pathogens vs. ~300 human pathogens; reflects ecological breadth and host barriers.

List the three main polysaccharides of the fungal cell wall

Cellulose, chitin, and β‑glucan.

Why are fungal cell‑wall components excellent drug targets?

Absent in mammals, essential for integrity, and accessible to extracellular drugs

Compare fungal ergosterol with mammalian cholesterol in membrane fluidity

Ergosterol modulates membrane order differently, affecting drug binding and permeability

Explain the mechanism by which β‑glucan synthase inhibitors (echinocandins) kill fungi

Block β‑1,3‑D‑glucan synthesis, weakening wall and causing osmotic lysis.

How does chitin content vary among fungal morphologies?

Chitin content varies significantly among different fungal morphologies, influencing structural integrity and function of the cell wall in species such as yeasts and filamentous fungi. Higher in septate hyphae for rigidity; lower in yeast for flexibility

Describe how hyphal tip growth is polarized at the molecular level

Actin cables direct vesicles carrying cell‑wall enzymes to the apex; Spitzenkörper organizes tips

What cellular role does the fungal vacuole play beyond storage?

Regulates turgor for hyphal extension, sequesters toxins, and recycles organelles via autophagy

Why is ergosterol biosynthesis a multi‑step drug target?

Multiple enzymes (e.g., lanosterol 14α‑demethylase) allow diverse inhibition points

Propose a fluorescent probe design to stain chitin in live fungi.

Conjugate a chitin‑binding lectin with a cell‑permeable fluorophore resistant to enzymatic degradation.

How do fungal septa regulate cytoplasmic flow?

Septal pores with Woronin bodies plug to isolate damaged hyphal compartments

Explain why fungal mitochondria are therapeutic targets

Unique respiratory proteins differ from humans, enabling specific inhibitors

What is the role of melanin in fungal cell walls?

Protects against UV, oxidative stress, and host defenses

Why are secreted proteases important for both nutrition and virulence?

Degrade host proteins for amino acids and aid tissue invasion

Describe how lipid rafts in fungal membranes influence drug uptake.

Microdomains rich in ergosterol concentrate transporters and may sequester drugs

Compare fungal cytoskeleton organization to that of mammalian cells.

Similar actin/microtubule components, but arranged for tip‐directed growth instead of cell migration

Explain what autophagy is and how it contributes to fungal survival under nutrient stress

Autophagy is a cellular degradation process that recycles cellular components and provides energy during nutrient scarcity, enhancing fungal survival by Recycles cellular components to maintain metabolism during starvation

What distinguishes fungal septin rings at hyphal bases?

Organize polarity sites and compartmentalize growth regions

Discuss the significance of fungal glycosphingolipids in pathogenesis

Modulate host immunity and facilitate adhesion/invasion

Propose an experiment to quantify ergosterol levels in drug‑treated vs. control fungi

An experiment could involve isolating fungal cells from both drug-treated and control groups, followed by using high-performance liquid chromatography (HPLC) or mass spectrometry to measure ergosterol concentrations. Comparing the ergosterol levels would determine the impact of the drug Azole on fungal membrane integrity.

Why might targeting fungal heat‑shock proteins be less specific?

Heat-shock proteins are conserved across many organisms, including humans, which can lead to off-target effects in fungal treatments. This lack of specificity may result in unintended consequences for host cells during antifungal therapy.

Outline the four stages of fungal infection (mycosis).

Entry → growth/colonization → penetration/toxin release → transmission.

Why is growth at ≥ 37 °C critical for human pathogenicity?

Enables survival in host core temperature

List three major fungal adhesins and their functions

HWP1 (hyphal attachment), ALS (agglutinin binding), INT1 (integrin mimic).

Explain how yeast‑to‑hypha morphogenesis aids tissue invasion in Candida albicans

Hyphae penetrate deeper tissues; yeast forms disseminate via bloodstream

Discuss the role of biofilms in device‑associated fungal infections

Biofilms resist drugs/immune clearance and seed persistent infections on catheters

Why does melanin enhance Cryptococcus virulence

Scavenges reactive oxygen species and shields from phagocytosis.

How do fungal capsules modulate host immune responses?

Inhibit phagocytosis, alter cytokine profiles, and mask PAMPs

Describe how secreted phospholipases contribute to pathogenesis

Disrupt host membranes to facilitate nutrient access and spread

Propose a genetic screen to identify new Candida virulence factors.

Create a transposon mutant library, assess mutants in murine infection model for attenuation.

Compare opportunistic vs. primary fungal pathogens in immunocompetent hosts.

Opportunistic infect only immunocompromised; primary can infect healthy individuals (e.g., Coccidioides).

What immune evasion mechanism does Aspergillus fumigatus use in lungs?

Masking β‑glucan with hydrophobin coat to avoid Dectin‑1 recognition

Explain the concept of “latent” fungal infections, using histoplasmosis as an example

Latent fungal infections occur when a pathogen remains in a dormant state within the host, often after an initial infection. In the case of histoplasmosis, the fungus can reside in macrophages without causing symptoms, reactivating under conditions of immunosuppression.

Describe how siderophore production aids fungal virulence

Scavenges iron from host, essential for fungal growth.

Evaluate targeting fungal iron uptake as an antivirulence strategy

May limit growth without killing, reducing selective pressure for resistance

How do fungal hydrolases facilitate deep tissue invasion?

Degrade extracellular matrix components, easing hyphal penetration

Propose a vaccine antigen based on fungal virulence factors

Recombinant HWP1 or β-glucan epitopes to block adhesion/trigger immunity

Discuss the trade‑offs of hyphal vs. yeast growth for Candida in bloodstream vs. mucosa

Yeast form resists shear in blood; hyphae better adhere to mucosal surfaces

Which innate receptor recognizes fungal β‑glucan?

Dectin‑1 on macrophages and dendritic cells.

Describe how Th17 responses contribute to mucosal fungal defense

IL‑17 drives neutrophil recruitment and antimicrobial peptide production

Explain antibody roles in controlling fungal infections

Lack neutrophils needed to clear inhaled conidia

How does the complement system aid in fungal clearance?

The complement system enhances opsonization of fungi, facilitating their recognition and clearance by phagocytes. It also leads to the formation of the membrane attack complex, which damages fungal cell membranes.

Why can excessive inflammation be harmful in fungal lung infections?

Tissue damage from neutrophil degranulation may worsen pulmonary function

Describe the role of macrophage polarization (M1 vs. M2) in fungal defense

M1 macrophages kill fungi via ROS; M2 promote tissue repair but may allow persistence

How do fungal PAMPs vs. DAMPs differ in immune activation?

PAMPs (β‑glucan, chitin) trigger PRRs; DAMPs (host‑derived) amplify inflammation

Evaluate risks of cytokine therapy (e.g., IFN‑γ) in fungal infections

Can boost clearance but also provoke immunopathology (cytokine storms) if uncontrolled

What factors drive the rising global antifungal market?

Aging populations and more immunocompromised hosts

Propose surveillance strategies for emerging pathogens like Candida auris

Routine hospital screening, molecular typing, and environmental sampling.

Compare incidence of superficial vs. invasive fungal infections globally

Superficial (1 billion cases) far exceeds invasive (> 1 million), but invasive carry higher mortality

Explain why fungal allergy (e.g., farmer’s lung) is occupationally significant

Chronic exposure to airborne spores leads to hypersensitivity pneumonitis

What is the gold‑standard for diagnosing invasive fungal infections?

The gold standard for diagnosing invasive fungal infections is obtaining cultures from normally sterile sites, such as blood or tissue samples.

What histological stain highlights fungal elements in tissue?

Gomori methenamine silver (GMS) and periodic acid‑Schiff (PAS).

Explain how MLST differs from ITS sequencing for fungal typing.

MLST uses multiple housekeeping genes for population structure; ITS is single‑locus barcode

Name the four major antifungal classes and their primary targets

Azoles (ergosterol synthesis), polyenes (ergosterol binding), echinocandins (β‑glucan synthase), 5‑FC (DNA/RNA synthesis).

Which enzyme is inhibited by azole antifungals?

Lanosterol 14α‑demethylase (Erg11), blocking ergosterol biosynthesis

List three commonly used azoles.

Fluconazole, Itraconazole, Voriconazole

How do polyene antifungals (e.g., Amphotericin B) kill fungal cells?

They bind ergosterol in the fungal membrane, form pores, and cause ion leakage

Name two polyene drugs.

Amphotericin B, Nystatin

What is the mechanism of action of echinocandins?

Non‑competitive inhibition of β‑1,3‑D‑glucan synthase, weakening the cell wall

 Give two examples of echinocandin antifungals

Caspofungin, Micafungin

Describe how 5‑Fluorocytosine (5‑FC) inhibits fungal growth

Converted by fungal cytosine deaminase to 5‑FU, which blocks DNA/RNA synthesis

Why is ergosterol an ideal antifungal target?

It’s unique to fungal membranes (absent in human cells), allowing selective toxicity

What fungal‑specific cell‑wall component do echinocandins exploit?

β‑1,3‑D‑glucan, which mammals lack

What major toxicity limits conventional Amphotericin B use, and how is it mitigated?

86. Nephrotoxicity—mitigated by lipid formulations (e.g., liposomal Amphotericin B)

Which antifungal is first‑line for fluconazole‑resistant candidemia?

An echinocandin (most often Caspofungin)

Describe the 4 main fungal body forms and give an example of each

Yeast (unicellular, e.g. Cryptococcus neoformans), hyphae (filamentous strands, e.g. Aspergillus fumigatus), mycelium (network of hyphae, as in mushrooms), sclerotium (hardened mycelial mass for overwintering).

What structural differences between fungal and mammalian cells are exploited by most antifungals?

Fungal cells have a rigid cell wall of cellulose, chitin, β‑glucan and use ergosterol in their membranes, whereas mammalian cells lack a cell wall and use cholesterol.

Explain heterotrophic absorption in fungi

Hyphal tips secrete extracellular enzymes that break down substrates; the resulting small molecules diffuse back into hyphae for nutrition

List four occupational fungal allergens and their etiological agents

Cheese washer’s lung (Penicillium casei); Malter’s lung (Aspergillus clavus); Maple‑bark stripper’s lung (Cryptostroma corticale); Wood‑pulp worker’s lung (Alternaria spp.).

Name two mycotoxins, their fungal sources, and primary clinical effects.

Amatoxins from Amanita phalloides → severe GI upset; Aflatoxin from Aspergillus flavus → liver damage and mutagenesis

Give two examples of endemic fungal pathogens, their diseases, and regions

Histoplasma capsulatum → histoplasmosis in the US Midwest/southern Ontario; Blastomyces dermatitidis → blastomycosis in the US Midwest/Ontario

What are three key fungal virulence factors?

Thermotolerance (growth ≥ 37 °C), adhesins (HWP1, ALS, INT1), and mechanisms to evade host defenses (melanin, capsule, biofilm). 

Which four genes (and lengths) are used for Histoplasma MLST?

ARF (470 bp), ANTI (412 bp), OLE (425 bp), TUB (278 bp).

How do the physical properties of A. fumigatus conidia aid infection?

Small, hydrophobic conidia disperse easily in air, resist high temperatures, and reach lower airways on inhalation

Describe Candida susceptibility to fluconazole

C. albicans usually susceptible; C. tropicalis and C. glabrata less susceptible; C. auris mostly resistant.

What is the global burden and fatality of aspergillosis?

 ~4 million ABPA cases/year; ~400,000 develop chronic pulmonary aspergillosis; invasive aspergillosis can have up to 90% mortality