Pathogenesis of Fungal Diseases and Introduction to Mycoses

What are the two morphologies of fungi?

unicellular and multicellular

Are fungi eukaryotes or prokaryotes?

Fungi are eukaryotes

What is the difference between yeast and mold?

Yeast = Uniceullar, Mold = Multiceullar

How do yeast reproduce?

Fission (budding): the mother cell pinches off → daughter cell

What do yeast colonies look like?

Round, pasty, mucoid

What structure does mold have?

Threadlike structures: hyphae

What is mycelium?

mass of filamentous hyphae

How are yeast and mold different when it comes to reproduction?

Yeast → Bud, Mold → Spores

What are the two types of asexual spores?

sporangiospore and conidia

How are sporangiospores formed?

In containing membrane: sporangium

What is the sporangium?

A sac holding spores together

How are conidia formed?

Naked, no membrane, look like fingers

Fungi that cause opportunistic infections are most severe in whom?

Immunocompromised people, Most immunocompetent can resist

What are the four primary pathogens that always cause disease even in a healthy host?

1. Blastomyces dermatitidis: blastomycosis

2. Coccidioides immitis: coccidiosis

3. Histoplasma capsulatum: histoplasmosis

4. Paracoccidiodes: paracoccidiomycosis

How are the four primary pathogens acquired, and what do they cause?

Acquired through inhalation of spores and causes respiratory infection

What is one characteristic that all four primary pathogens share?

Dimorphic

What does “dimorphic” mean?

Exist in two forms

What are the two forms that the four primary pathogens possess?

Saprobic and Parasitic

What is the saprobic form?

Mold form found in nature, exists at 25°C, filamentous

What is the parasitic form?

Yeast-like, spherical form in enriched media or in host, exists at 37°C.

Where is the saprobic phase found?

Soil/environment, 25°C

What does the saprobic form produce and cause?

Produce airborne “conidia” spores that cause infection

Where is the parasitic phase found?

Inside the body at 37°C

How does the parasitic phase reproduce?

Asexually in host (budding)

What property allows fungi to better adapt to hosts and to survive?

Ability to be dimorphic

What is the environment for Blastomyces dermatitidis?

Decaying matter

Is patient-to-patient transfer of Blastomyces dermatitidis possible?

No patient-to-patient transfer

Is lab acquisition of Blastomyces dermatitidis possible?

Lab acquisition is possible

What are the two forms of Blastomyces dermatitidis?

Spherical yeast and Filamentous Hyphae

What form of Blastomyces dermatitidis infects humans?

spherical yeast at 37°C

What are the filamentous hyphae form of Blastomyces dermatitidis?

white-tan filaments at 25°C

What does the filamentous form of Blastomyces dermatitidis produce?

Conidia (spores)

How does the spherical (yeast-like) form of Blastomyces dermatitidis reproduce?

By budding

What does the spherical form of Blastomyces dermatitidis look like?

Figure 8, peanut, snowman under microscope

How does infection of Blastomyces dermatitidis occur?

Humans inhale conidia, which attach to the alveolar mucosa (lungs) and convert to spherical/yeast form depending on the temperature

What is thermal dimorphism?

Fungal pathogens can convert to spherical/yeast form depending on the temperature

What does Blastomyces dermatitidis cause?

Lung inflammation, immune cells recruited, organism often escapes and can become disseminated spreads to skin

What pathogen causes blastomycosis?

Blastomyces dermatitidis

What is the disease progression of blastomycosis?

Pulmonary infection, then Chronic cutaneous infection

How does a pulmonary infection from Blastomycosis begin?

Mild flu-like → resembles pneumonia → fever → pulmonary lesions → respiratory failure

What does the severity of pulmonary infection from Blastomycosis depend on?

Exposure and immune response

How is chronic cutaneous infection from Blastomycosis spread?

From lungs to skin, with or without pulmonary symptoms

What is also seen along with a chronic cutaneous infection from Blastomycosis?

skin lesion that is papular, crusty, irregular borders

Where is Coccidioides immitis found?

Soil and bat and rodent droppings

What is the most virulent human mycotic pathogen?

Coccidioides immitis

What are the two forms of Coccidioides immitis?

Mold-like form and spherical yeast-like form

What are the hyphae like, and what is produced by Coccidioides immitis?

Separated (divided), filamentous and producing barrel-shaped arthronidia

What are arthroconidia?

Spores break off from hyphae

How are humans infected by Coccidioides immitis?

Inhaling arthroconidia: small enough to enter alveoli, very difficult for body to clear

Why are arthroconidia anti-phagocytic?

Have a hydrophobic outer layer

What is another name for Coccidioidomycosis?

Valley Fever

What is the disease progression of Coccidioidomycosis?

inhale spores → spherical form → crosses respiratory mucosa → blood → disseminates in the body

How much conidia is needed to cause infection?

A few

Are antifungals needed for primary coccidiomycosis?

Resolves without therapy

Is there protection after infection of primary coccidiomycosis?

Strong protective immunity after infection

Are antibodies made after a primary coccidiomycosis infection?

Made to major surface glycoprotein (SOWgp)

How does secondary coccidiomycosis occur?

primary doesn’t clear→ progressive pulmonary

Where is Histoplasma capsulatum found?

Soil with high nitrogen content

What are the two thermally dimorphic forms of Histoplasma capsulatum?

Budding yeast and filamentous mold-like forms

How are macroconidia and microconidia created?

Slow-growing filamentous turns into tan-brown filaments (after several days of growth)

Can you inhale macroconidia or microconidia?

Macroconidia = cannot inhale, Microconidia = can inhale in lungs

Where can someone be exposed to histoplasmosis?

Exposure to bird roost, caves (bats), decaying buildings, and excavation sites

What is the disease progression Histoplasmosis?

Inhale microconidia → convert to yeast form in lungs; single conidia cause infection: more usually necessary

Can macrophages kill conidia in histoplasmosis?

Can kill conidia (spores) but not yeast forms

How do yeast forms survive in macrophages?

Increases pH of phagosome → enzymes lose function

Yeast cell wall is altered → resistant to killing enzymes

What happens after Histoplasma capsulatum is inhaled?

phagocytosed by macrophages

Are there symptoms of Histoplasmosis?

Most are asymptomatic: Symptoms show up 3-17 days after infection, which include fever, dry non-productive cough, and chest pain. Only fatal if disseminated

Does everyone get sick from opportunistic fungal pathogens?

Most immunocompromised can resist; it is most severe in immunocompromised.

What is the primary importance in determining the pathogenicity of opportunists?

State of host

Are opportunistic fungal pathogens easy or difficult to diagnose?

Very challenging to diagnose because of:

• Complexity of patients at risk

• Underlying factors that create risk

• Number of possible fungi

Why are opportunistic fungal pathogens hard to treat?

Many arent susceptible to common antifungals

What are some host predisposing factors that increase the risk of fungal infections?

Chemotherapy, Corticosteroids and AIDS are immunosuppressive.

How do we classify fungal opportunists?

Normal flora: fungi that produce disease in debilited hosts OR Saprophytes normally considered contaminants, that may produce disease in debilitated hosts.

Why are fungal infections are very difficult to diagnose properly?

Must determine if cultured isolate from patient is significant or if it is a contaminat

What are the most studied and best understood causes of opportunistic mycoses?

1. Candida albicans

2. Cryptococcus neoformans

3. Aspergillus fumigatus

Which fungal pathogen is the most common opportunistic fungi?

Candida

What is the path progression of Candida?

colonize mucosa →enter bloodstream via breaks, catheters etc. → invade deeper tissues: liver, spleen, heart, brain

What contributes to pathogenicity of Candida?

Hydrophobic cell surface: adhere to broad range of tissues: many adhesions and non specific interactions (electostatic)

What property contributes to pathogenicity of Candida?

Dimorphic: yeast and hyphal forms: regulated by temperature and pH

What is thigmotropism?

Hyphal sense of touch, growth on irregular surfaces, have to force Candida to grow like this

What are some chemical properties that contributes to pathogenicity of Candida?

proteinases and enzymes: damage host cells and host defences

What is a physical property contributes to pathogenicity of Candida?

phenotypic switching: rapidly changes forms: aids in survival

What are the two dimorphic forms of Candida?

oval, yeast-like shape and hyphal form (not C. glabrata)

What colony morphologies can Candida change to?

smooth white domed colony (yeast) → fuzzy hairy colonies (hyphae)

Where does Candida spp. normally colonize in humans and animals?

entire GI tract

Are Candida spp. infections endogenous or exogenous?

Most endogenous breach in host barriers BUT some exogenous infections happen through contaminated catheters, valves, healthcare workers transmit to patients

Almost all Candida infections are which species?

C. albicans

Which strain of Candia is more common in older people?

C. auris, glabrata

Which strain of Candia is more common in younger people?

C. parapsilosis

What is Candidiasis clinically associated with?

Implanted indwelling devices and antibiotic use, Almost any organ infected, superficial cutaneous → disseminated: liver, kidney, brain (50% mortality)

What is the most common infection of Candidiasis?

Vaginal

What ar other common infection of Candidiasis?

GI, mucosa, Throat = Oral thrush occurs during immunosuppersion

What is the interaction between vaginal bacteria and candida?

Imbalance between vaginal bacteria and candida, “white cottage cheese” patches on surface: bleed when scraped

What happens to the skin during Candidiasis?

Itchy (pruritic) rash on moist, folded skin

What happens to the bladder during Candidiasis?

infection only seen with cather use

What makes you more susceptible to contracting/developing Candidiasis?

central vein catheter, Candida colonization of other body sites, acute hemodialysis

50% of Candida auris isolates are resistant to what?

Disinfection and multiple antibiotics

Why does it pose a risk that Candida auris can colonize skin asymptomatically?

Infection/transmission in healthcare settings

Where are Candida auris infections found?

bloodstream, wound, ear infections