Mycology

General Characteristics

  • Eukaryotic

  • Sterols

  • Chemoheterotrophs

  • Aerobes

  • Neutral pH

  • Saprophytic

    • Living on dead/decayed organic matter

  • Acquire food by absorption

  • Produce sexual or asexual spores (conidia)


Candida (yeast) Cell Wall

  • Contains:

    • Mannoproteins (protein): cell stability

    • Chitin (polysaccharide): structural integrity

    • Glucans (polysaccharide): structural integrity

Cryptococcus Cell Wall

  • Capsule (polysaccharide): virulence factor, protects against and interferes with host immune cells

  • Chitin: structural integrity

  • Glucans: Structural integrity

  • Melanin (phenolic compound): virulence factor, protects against and interferes with host immune cells


Aspergillus Cell Wall

  • Glactomannan (polysaccharide): released during tissue invasion

  • Glucans and Chitin: Structural integrity


Molds:

  • Multicellular

  • Filamentous form of fungi consisting of thread-like filaments

  • For fuzzy colonies

Yeast:

  • Unicellular

  • Produce circular. Restricted, pasty mucoid colonies

Dimorphic:

  • Exhibit either yeast or mold phase


Filamentous Fungi

  • Composed of hyphae: microscopic filaments

  • Forms mycelium: network of hyphae

  • Aerial: hold reproductive structures

  • Vegetative: absorb nutrients

  • Hyphae

    • Shape: tubular

    • Septate- cell wall breaks

      • Frequent perpendicular cross-walls = septate

      • Infrequent = sparely septate

    • Pigmentation

      • Hyaline (nonpigmented)

      • Dematiaceous (dark, pigmented hyphae, presence of melanin)

Unicellular Yeast

  • Capable of reproducing asexually/sexually

    • Asexual reproduction:

      • Budding

      • Binary fission


Fungal Spores (Conidia)

  • Role:

    • Dispersal

    • Survival (low metabolic state)

      • Dormant state:

        • Germinate if conditions are favorable

  • uni/multicellular

  • Varies in size, shape, color


Spectrum of Disease

  • Superficial

  • Cutaneous

  • Mucosal

  • Systemic


Fungal Populations in Humans

  • Oral Activity

    • Candida

    • Aspergillus

    • Malassezia

    • Cladosporium

    • Saccharomyces

    • Fusarium

    • Penicillium

    • Pichia

    • Rhodotorula

  • Lungs

    • Aspergillus

    • Cladosporium

    • Penicillium

    • Candida

  • Urinary Tract

    • Candida

    • Saccharomyces

    • Malassezia

  • Vagina

    • Candida

    • Saccharomyces

    • Pichia

    • Cladosporium

    • Phodotorula

  • Breast Milk

    • Malassezia

    • Davidiella

    • Sistotrema

    • Penicillium

  • Skin

    • Malassezia

    • Aspergillus

    • Candida

  • Intestine

    • Candida

    • Saccharomyces

    • Aspergillus

    • Cyberlindnera

    • Fusarium

    • Malassezia

    • Rhodotorula

    • Wallemia

    • Cladosporium

    • Penicilium

Classification

  • Clinical Microbiology based on mucoses (fungal diseases)

    • Superficial

      • Confined to outermost “dead” layer of skin/hair

    • Cutaneous

      • Affects keratinized layer of skin, hair, nails

    • Subcutaneous

      • Deeper skin layers 

    • Systemic

      • Affects internal organs/deep tissues of body

    • Opportunistic 

      • Found in immunocompromised people


Innate Resistance

  • Body temp = too high for fungi to adapt/mutate for

  • Exposed to a huge amount of spores


Mode of Transmission

  • superficial/cutaneous

    • Person to person

    • Animal too human

  • Subcutaneous

    • Through the skin (via injury)

  • Deep mycoses

    • Opportunistic growth in immunocompromised

    • Inhalation of spores/conidia



Bacterial

Viral

Fungal

Increased WBC

Increased WBC

Increased WBC

Neutrophils

Lymphocytes

Lymphocytes and Monocytes

Increase in total protein (Albumin)

Moderate increase in total protein

Mod-marked increase in total protein

Marked decrease in glucose

Normal glucose

Normal to low glucose

CSF lactate >35 mg/dl

Lactate Normal

Lactate >25 mg/dl


Specimen Collection/Transport

  • Selection based on

    • Information obtained from clinical examination/radiographic studies

    • Consideration of most likely fungal pathogens

    • Collect aseptically

    • Collect adequate amount of material

    • Submit sterile leak-proof container

    • Store in 4C


Specimen Handling

  • Process under biological safety cabinet

  • ID methods:

    • Direct microscopy

    • Biochemical tests

    • Susceptibility testing

    • Automated identification systems

    • Histopathological methods

    • Immunologic methods

    • Molecular methods


Culture Time/Conditions

  • Time

    • Yeast: Growth detected 48-72 hours

    • Mold: 4-6 weeks

  • Temp

    • Incubation for fungals = 25-30C

    • Dimorphic fungi

      • Mold temp (30C) 

      • Yeast phase (37C for 7-14 days)


Fungal Culture Media

  • Battery of media should use:

    • Enriched media

      • Ensure growth of fastidious thermally dimorphic fungi

    • General purpose media

      • Ensure growth of variety of molds and yeast

        • No antimicrobial agents

        • Antibacterial 

          • Chloramphenicol

          • Gentamicin

        • antibacterial/antifungal 

          • Cycloheximide

            • May inhibit Cryptococcus neoformans, Mucorales, Candida sp. Aspergillus sp, and Histoplasma


Colonial Morphology

  • Texture: height of aerial hyphae

    • woolly/cottony (High/dense)

    • Velvety (low)

    • granular/powdery (flat/dense)

  • Color: Surface and reverse

  • Topography: designs of kills/valleys


Microscopy

  • Stains/reagents

    • Lactophenol cotton blue

      • Kills any organisms

      • Lactic acid acts as clearing agent

      • Preserves fungal structures

      • Stains chitin in fungal cell walls

    • Potassium hydroxide

      • 10 to 20% solution dissolves keratin

    • Calcofluor white

      • Fluorescent stain

      • Binds to cellulose and chitin in fungal walls

    • Gram stain

      • Stain gram positive

  • ID

    • Observe asexual reproductive structures (sporangiospores/conidia)


Antifungal Agent

  • Fungistatic (slows down growth) or Fungicidal (kills fungus)

  • Systemic active agents

    • Polyenes

      • Weakens cell membrane

        • Kills cell due to loss of cell integrity

      • Bindings to ergosterol produce little holes in the membrane

      • Problem: binds to cholesterol

        • Can kill human cells

      • Broad spectrum of activity

      • Fungicidal

      • Main adverse effect: nephrotoxicity (kidney damage)

    • Azoles

      • Attacks cell membrane

        • Prevents ergosterol to be produced

        • Weakens cell membrane

      • Fungistatic to yeast

      • Fungicidal to mold

    • Echinocandins

      • Attacks cell wall

      • Inhibits glucans, affecting the cell’s integrity

      • Low toxicity

      • Fungicidal (Candid) and fungistatic (Aspergillus)

    • Flucytosine

      • Prevents DNA, RNA, protein synthesis

        • Prevents fungal cell wall from forming

      • Fungistatic

      • Limited spectrum

        • Candida, Cryptococcus select dematiaceous molds

        • Used in combination with another antifungal (due to resistance)

    • Allylamines

      • Inhibit squalene

        • Decreases ergosterol and increases squalene in cell (toxic to cell)

      • Broad spectrum

      • Fungicidal

  • Topical Active Agent

    • Creams 

    • Lotions

    • Ointments

    • Powders

    • Sprays

    • Treats superficial, cutaneous, mucosal infections

  • Topical vs. Systemic depends on:

    • Status of host

    • type/extent of infection


Antifungal Resistance

  • Resistance develops slowly 

  • Involves alteration of cellular structures/functions

  • Mechs: 

    • Biofilm formation (reduces penetration of antifungal)

    • Efflux pumps (reduces accumulation of medicine)

    • Target alterations/mutations

    • Overexpression of target (overproduction of enzyme)