how fungus causes disease

What are the general characteristics of fungi and how are fungi classified?

Fungi are eukaryotic organisms with chitin in their cell walls, ergosterol in their membranes, and reproduce via spores. They are classified by morphology (yeasts, molds, dimorphic), mode of reproduction (sexual/asexual), and molecular taxonomy.

What are the major fungal divisions and which are more likely to cause disease in humans?

Divisions:

• Mold (filamentous, multicellular)

• Yeast (unicellular)

• Dimorphic (switch between yeast and mold).
  Dimorphic fungi are more often primary pathogens, while yeasts and molds are mostly opportunistic.

What is the difference between yeast and mold lifecycles and how do haploid/diploid stages differ?

Molds often exhibit haploid (n) stages with sexual/asexual spore formation. Yeasts like Saccharomyces cerevisiae can switch between haploid and diploid stages. Diploid cells undergo meiosis to form spores; ploidy affects genetic diversity and resilience.

How do spores form in yeasts and molds, and which group is more associated with spore production?

Molds are primarily associated with spore production (conidia, sporangia) through asexual or sexual reproduction. Yeasts can form spores (e.g., Saccharomyces) but it is rare. Yeast has to do phenotypic switching to make spores. Molds use spores for dissemination and survival.

Are there multicellular yeasts and why are they clinically significant?

Yes, under certain conditions yeasts like Candida albicans can form pseudohyphae or true hyphae.

This transition enhances tissue invasion and immune evasion, contributing to pathogenesis.

What are the general structural components of mold and how does mold growth occur?

Molds consist of hyphae forming a mycelium. Growth occurs by apical extension of hyphae and branching, enabling surface colonization and nutrient absorption.

How does sexual reproduction occur in molds via hyphal mating?

Opposite mating types (+/-) of hyphae fuse to form a zygospore or other sexual structures, undergoing meiosis to generate genetically diverse spores.

What happens during the vegetative stage of fungi?

In this stage, spores germinate under favorable conditions to form active hyphae or yeast cells, initiating colonization and infection.

How do primary fungal pathogens differ from opportunistic ones?

Primary pathogens (e.g., dimorphic fungi) can infect healthy individuals. Opportunistic fungi (e.g., Candida, Aspergillus) require compromised immunity to cause disease.

Why are spores important in disease progression and how do they initiate infection?

Spores resist environmental stress, allowing inhalation or skin contact to initiate infection upon germination, especially in immunocompromised hosts.

Why do host factors play a significant role in fungal infections?

Fungal infections often depend on host immune suppression, antibiotic use, medical devices (e.g., catheters), neutropenia, or HIV. Most fungi are opportunistic and require weakened defenses to cause disease.

Why are fungi largely considered opportunistic infectious agents?

Fungi typically do not infect healthy individuals. They exploit weakened immune systems, making immunocompromised patients their main targets.

Why are fungi generally not considered primary pathogens?

Fungi lack aggressive virulence factors found in bacteria or viruses. Most cannot breach intact host barriers or evade robust immune responses without predisposing conditions.

Are fungal infections contagious? If not, how are people exposed?

Fungal infections are not typically contagious. Exposure occurs via environmental spores (soil, decaying matter, air) or endogenous flora overgrowth (e.g., Candida).

What makes dimorphic fungi unique and why are they considered primary pathogens?

Dimorphic fungi switch from mold (environment) to yeast (host) at body temperature. This switch supports survival in humans and makes them true/primary pathogens (e.g., Histoplasma, Blastomyces).

How do dimorphic fungi disseminate from the lung?

After inhalation and lung colonization, fungi may spread hematogenously to skin, bones, CNS, or organs, depending on the species and host immunity.

What types of clinical spores are associated with fungal disease?

- Conidia (e.g., Aspergillus)

• Arthroconidia (Coccidioides)

• Blastoconidia (Candida)

• Sporangiospores (Mucor, Rhizopus)
  These are infectious forms involved in pathogenesis.

What are the genus names of clinically relevant fungi?

Candida, Aspergillus, Cryptococcus, Histoplasma, Coccidioides, Blastomyces, Sporothrix, Stachybotrys, Mucor, Rhizopus.

What are the unique mechanisms of key fungal pathogens?

• Candida: phenotypic switching, pseudohyphae, biofilms

• Aspergillus: conidia inhalation, mycotoxin production

• Stachybotrys: toxic black mold, colonizes lung, produces mycotoxins

• Cryptococcus: thick capsule, CNS dissemination

• the ones below are dimorphic

• Coccidioides: spherule formation, desert exposure

• Histoplasma: intracellular survival in macrophages

• Blastomyces: broad-based budding

• Sporothrix: traumatic implantation, rose gardener's disease

How do invasive fungal infections differ from dermal/subcutaneous ones?

• Invasive: systemic, often from respiratory entry, can affect blood/organs

• Dermal/Subcutaneous: from trauma or skin breach (e.g., Sporothrix), localized

How can primary diseases contribute to secondary fungal infections?

Conditions like cancer, HIV, or transplant immunosuppression can lead to fungal overgrowth (e.g., Candida, Aspergillus) due to reduced immunity.

What is the effect of mycotoxin exposure from fungi like bread mold?

Acute ingestion or inhalation of mycotoxins (e.g., from Rhizopus or Stachybotrys) can cause systemic toxicity, allergic reactions, or respiratory inflammation.

What are the effects of Stachybotrys colonization and mycotoxin production in the lungs?

Chronic exposure causes persistent inflammation, immune dysregulation, and respiratory illness, especially in enclosed, moldy environments.

How does aflatoxin-producing Aspergillus affect the lung and liver?

Aflatoxins (especially from A. flavus) are hepatotoxic and carcinogenic. Inhalation can lead to chronic lung inflammation; ingestion affects the liver.

How does Candida disseminate in bloodstream infections?

It translocates from the GI tract or catheter biofilms into the bloodstream, causing candidemia, sepsis, and possible organ failure.

What is phenotypic switching in Candida and its clinical importance?

Candida switches between yeast, pseudohyphae, and hyphae. This enhances immune evasion, tissue penetration, and biofilm formation, increasing virulence.

How does the innate immune system respond to fungi?

Phagocytes (macrophages, neutrophils) ingest fungal cells/spores. Chronic exposure may lead to granuloma formation and cytokine-mediated inflammation.

How does chronic spore exposure (e.g., Stachybotrys) lead to disease?

Persistent inhalation triggers immune activation, hypersensitivity pneumonitis, and may contribute to asthma or chronic lung inflammation.

How can Candida, a normal yeast flora, cause invasive and dermal infections?

Antibiotic use, immunosuppression, or mucosal damage can cause Candida overgrowth, leading to skin, mucosal, or bloodstream infections.

What fungal infections are associated with hospitals?

Candida BSI, Aspergillus lung infections in ICUs, device-related infections from catheters, prosthetics, and ventilators.

How does phenotypic switching in Candida lead to disease?

It enables morphologic changes that help evade immunity, form biofilms, and adapt to different host environments, increasing invasiveness.

What is indirect virulence and what are common fungal virulence factors?

Indirect virulence includes host-damaging immune responses. Common factors: capsule (e.g., Cryptococcus), enzymes, adhesins, biofilms.

How do saprobic, commensal, and parasitic fungi differ and transition between forms?

• Saprobic: live on decaying matter (e.g., dimorphic fungi in environment)

• Commensal: (growing on us in a healthy manner) harmless colonizers (e.g., Candida)

• Parasitic: cause disease when conditions allow
  Stress or immune suppression can drive these transitions.

What are key structural features of fungi and their treatment targets?

• Yeast: single cells, budding

• Mold: hyphae, spores
  Treatment targets: cell wall (β-glucans), membrane (ergosterol)

What are unique yeast drug targets, common targets, and how do antifungals work?

• Unique: β-glucan synthase (echinocandins)

• Common: ergosterol (amphotericin B, azoles)
  Azoles inhibit ergosterol synthesis, polyenes bind ergosterol directly.