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3.5.12 - Intro to Mycology and Pathogenic Fungi
3.5.12 - Intro to Mycology and Pathogenic Fungi
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Biology
Graduate
03/17/2012

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Term
What part of the "food chain" are fungi?
Definition

Decomposers, the best in the environment.

They break down organic material for a benefit, they need the organic molecules to survive and use them for their individual benefit.

Term
Diversity of Fungi
Definition

Very diverse eukaryotic organisms.

Can be unicellular or multicellular.

Ex: Spores of Candida Albicans (uni)

*Present as normal floura on our skin and mucous membranes. We normally see infection candida.

Ex: Almanita Muscaria

*A red, poisonous mushroom (multi)

Term
Instead of cholesterol in the cell membrane, fungi have...
Definition

Ergosterol.

Important for targeting fungi specifically even though they are eukaryotic.

Term
Name the three unique components to the cytoplasmic membrane.
Definition
Mannan, Glucans and Chitins
Term
Mannan
Definition

When combined with protein forms 'mannoprotein'.

They are immunogenic, meaning they induce an immune respons. We detect the fungal organism on the basis of that.

Often used to sero-group the fungal pathogens specifically.

Term
Chitin
Definition

Composed of long, unbranched chains of poly-N-acetylglucosamine.

Inert and rigid, giving the toughness of fungal organisms.

Makes fungi ubiquitious, so they can survive in adverse environmental conditions.

Offers support and integrity to the fungi.

Term
Glucan
Definition

Polymer of glucosyls made up of carbohydrates.

Provides structural integrity.

Term
Metabolism of Fungi
Definition

Very diverse.

Heterotrophs: rely on carbon (from glucose), nitrogen (from organic nirogen and ammonia), nucleic acid.

All of these resources have to be provided for externally. Aerobes and facultative anaeurobes (anaerobic if needed). NO FUNGI ARE STRICTLY ANAEROBES

Term
Examples of facultative anaerobes in fungi
Definition
E-Coli, salmonella, shigella (collectively grouped as enterobacteria because they're all found in the digestive system)
Term
How do fungi function with no digestive system?
Definition

They secrete enzymes outside of the body (exo-enzymes) to break down complex molecules to simpler form and then they acquire ita nd utilize it for their metabolism.

Note: Fungi lack photosynthetic energy producing mechanisms.

Term
Growth requirements for fungi
Definition

Grow at various temperatures

(Low --> High: Psychrophilic, Mesophilic, Thermophilic)

Wide range of pH: 2.2 - 8.5

(clinically important fungi at 6.5-7.0)

80-90% humidity

Prefer the dark (photosensitive)

Aeriation: Aerobes and facultative anaerobes

Term
Fungi may reside in nature and in the host tissues in these three different forms...
Definition
Yeast, Mold (hypa or mycellium), Dimorphic
Term
Yeast Morphology
Definition
Unicellular, circular or eliptical structures
Term
Mold (hypha) Morphology
Definition
Intertwining branched elements
Term
Dimorphic Fungi Morphology
Definition

Take on the shape of yeast and/or mold.

At ambient temperature, they are mold (hypha).

When they enter the body they change shape to assume circular/elliptical shape of yeast.

Term

We must know the dimorphic fungi. They are...

(YOU WILL BE TESTED ON THIS)

Definition

"Body Heat Changes Primary Shape"

B: Blastomyces dermatidis

H: Histoplasma capsulatum

C: Coccidioides immitis

P: Paracoccidiodis Brasilienisis

S: Sporothrix Schenkii

Term
Sexual Reproduction in Fungi
Definition

Two haploid cells fuse to become diploid, followed by meiosis.

Explains how they produce daughter cells with a haploid nucleus.

Term
Asexual Reproduction in Fungi
Definition

Can undergo fission from one cell into two

 (aka. Binary fission)

Can undergo budding; the yeast will sometimes give rise to a bud which gradually grows and separates out form the mother to become a new cell (blastoconidiosis). Hypha separate from the mother to become a new hypha.

Term

Difference between a fungal and bacterial spore

(Testable Point)

Definition

Fungal Spore --> Develops a germ tube (think candida always) --> GT elongates to produce a hypha --> Hypha grow and intertwine to become mycellium

 

Bacterial spore is a protective form that gives it the ability to withstand adverse environmental conditions (ex:  bacillus and clostridium, gram positive rods)

Term
Portions of fungi
Definition

Vegetative hyphae: The part that goes deep down to acquire nutrients

Aerial hyphae: The part in the air

Note: Hyphae can either be septate or non-septate (fragmented or not)

Term
Morphology of Conidiophores
Definition

Stalks with conidia at the end; these are elements of asexual reproduction.

Some are large (macroconidia), some are small (microconidia).

 

Term
Arthroconidia
Definition

Condiophores that are barrel shaped and joined, specifically referring to coccidia adimycosis (in the environment).

It has a respiratory manifestation.

Arthroconidia in the tissue (skin) we know it's a case of dermatophyte infection (fungal organisms that cause superficial skin infection).

Affects skin, hair and nail.

Term
Morphology of Hyphae of Aspergillus Fumigatus
Definition

This fungal pathogen can form allergic or invasive aspergilosis (mortailty is 90% or above).

Lab will know by looking at the hyphas morpholgy.

"Dicor-somethingly branching" - Each oen will split into two.

The hyphae are also septate; there are lateral walls present.

Term
Morphology of Hyphae Candida Albicans
Definition

Circular things are yeast, with hypha like structures.

Pseudohypha of candida: Will show constriction at each septa, as if they are separating from each other.

*This is the important way we will distinguish candida, which are described as having a germ tube (very characteristic description).

Term

Spores generated through sexual reproduction

(Not as important, but KNOW THE NAMES)

Definition

Zygospores: Thick walled sexual spores

Ascospores: Spores born internally in a sac like structure known as an ascus

Basidiospores: Born externally on a club shaped structure.

Term
Classifications of Mycoses used in clinical medicine
Definition
Superficial, subcutaenous, deep and opportunistic
Term
Reproduction/budding of yeast
Definition

Asexual.

A point on the yeast is becoming softened and the cytoplasm is bulging out.

The nucleus is undergoing mi tosis and is going to split in two.

One of the two is going to the bulged cytoplasm.

The cell wall keeps going and it buds off the mother cell.

Daughter cell has the same genomic characteristic as the mother.

Known as budding: Bastoconidiosis

Term
Cryptococcus Neoformans
Definition

Respiratory pathogen.

Identified based on the budding yeast.

Will be seen in immunocompromised inviduals as meningioencephalitis

(traditionally seen in HIV/AIDs patients)

Term

Paracoccidioidis Brasiliensis Yeast

(Not as high yield on the boards)

Definition

Multiple budding.

Steering wheel appearance.

Term
Yeast grown on a culture media
Definition

White, creamy, large colonies indicate candida.

We use morphology rather than culture, because a lot of yeast have a similar growth rate.

Term
Taxonomy of Medically Important Fungi: Zygomycota
Definition

Stuff he talked about:

Sexually reproduce via zygospores.

Genus mucor, rhizopus, absidia - dangerous pathogens.

Diabetic ketoacidotic and leukemic pateints inherit them and develop encepalopathy.

When describing the pathogen, we say they have "no repsect for anatomic barriers" because they break through bones and invade the frontal lobe of the brain.

Near 100% mortality.

Stuff on slide:

Asexual reproduction through sporangiospores.

Term
Taxonomy of Medically Important Fungi: Ascomycota
Definition

Stuff he said:

N/A

Stuf on slide:

Sexual reproduction through ascospores within sacs or asci.

Asexual reproduction through blastoconidia or conida on condiophores.

Genus: Microsporum, aspergilius, trichophyton, histoplasma, blastomyces

Term
Taxonomy of Medically Important Fungi: Basidiomycota
Definition

Stuff he said;

Reproduction through basidia.

Stuff on slide:

Asexual reproductiongthrough conidiogenesis.

Genus: Cryptococcus.

Term
Taxonomy of Medically Important Fungi: Deuteromycota
Definition

What he said:

No sexual reproduction.

Ex: Candida - When an individual becomes immunocompromised, it will cause an infection (oral thrus, diaper rash, esophagitis, gastritis, etc.). Can cause a huge number of clinical representation.

What's on the slide:

Asexual reproduction through conidiogenesis.

Genus candida, malasezia, trichosporon, coccidoidis, paracoccidiodis, penicillum, epidermophyton.

Term

Classification of Fungal Infections: Superficial

(WILL BE TESTED ON THIS)

Definition

Dermophytes: Skin, hair and nails

*Epidermophyton: Skin and nails

*Microsportum: Skin and hair

*Tricophyton: Involves skin, hair and nails.

Infection is described as tineasis; caused by dermatophytes.

They like keratinized tissue.

Ex of one that likes non keratinized tisue is candida

Term

Classification of Fungal Infections: Subcutaneous

(WILL BE TESTED ON THIS)

Definition

Sporothricoses: Rose garden disease

*Patients will work in a garden and come down with subcutaneous ulcers on their skin, most likely in the upper extremity. It won't go away, but will come and go.

*They travel through lymphatics to other regions (satellite lesions).

*Can be caused by candida (ex: diaper rash)

Term

Classification of Fungal Infections: Systemic

(WILL BE TESTED ON THIS)

Definition

Deeper structures.

Ex: Aspergillus, pneumocystis.

Term

Classification of Fungal Infections: Opportunistic

(WILL BE TESTED ON THIS)

Definition

Fungal infections only invovle the immunocompromised inviduals.

Ex: pneumocystis causing pneumonia in AIDs patients

Term
Examples of Superficial and Subcutaneous Fungal Infections
Definition

Tinea Pedis - Cutaneous infection of the foot caused by Trichophyton

Fungal infection of the nail - Caused by Dermatophytes (Tricophyton or epidermophyton)

Candidiasis Albicans - Diaper rash; infection of skin and subcutaneous tissue.

Sporothrix schenkii - Subcutaneous ulcer with an indurated (deep) base, meaning that subcutaenous tissue is involved.

Term
Systemic Mycosis
Definition

Invasive aspergilosis.

90% mortality; not fun.

Amphotericin B is given, but does not work.

Term

Systemic Mycosis

***Very high yield pathogen***

Interstitial pneumonia

(WE WILL BE TESTED ON THIS)

Definition

Looks like ground glass, hazy on a chest x-ray

There are white streaks from the hilum to the periphery.

Description of interstial pneumonia

Pathogen: Pneumocystis

Term

Factors predisposing fungal infections

(IMPORTANT SLIDE, NEED TO KNOW IT)

Definition

Steroid hormone therapy

Prolonged antibiotic treatment

Long term treatment with H2 receptor blocking agents (decreases acidity leading to the survival of pathogens)

Diabetes melitus

High starch or sugar containing diets

Compromised immune system due to HIV/AIDs

 

Term
Adaptive Immunity
Definition

Lymphocytes.

T- Cells - Offer cell mediated immune response

*Thymus

B-Cells - Offer humoral response

*Plasma cells secrete antibodies

*Have surface receptors that respond to antigens

Term
Cell mediated immune response to fungal infections
Definition

Phagocytes (Macrophages and neutrophils)

*Differentiated tissue monocytes (microglia in brain, Kupfer cells in liver, macrophages or histiocytes in tissue)

*Eat fungal pathogens, but fungi keep replicating (they survive because of their cell wall)

*Fungus specific helper T-cells (CD4) produced IL-2 and IFN-gamma which activate macrophages and help them elminate pathogenic fungi.

Term
Steps to make a diagnosis
Definition

Scrape the tissue.

Use 10% KOH to get rid of everything but the fungus.

Expect to see hpypha under a microscope.

We can use H&E, but some prefer silver staining, can also use cotton blue staining.

*Very conclusive on pneumocystis infection

Typical culture media is saburaud dextrose agar media or blood agar with antibiotics

Term
Serology is not popular for fungal infection. But here's an example:
Definition

Sometimes we do it to detect not the antibody, but the antigen of the cryptococcus neoformins something found in HIV patients by checkins CSF: latex agglutination test

*The latex particle is going to have the antibody coated on, patient CSF has polysaccharide antigen, put them together and look for clumping

*Antigen and antibody will cross link, become heavy and settle as a visible clumping (agglutination)

Term
DNA probes
Definition
Aids in rapid identification, but it is not available in most of the clinical laboratories
Term
Antifungal Drugs
Definition

Target ergosterol found in the cell membrane.

*We can target it to either break down or inhibit its synthesis.

*There's only one that doesn't have ergosterol: pneumocystis carinii/iroveci

*Ergosterol is targeted by polyenes, azoles, allyamines

*Flucocytosine inhibits nucleic acid synthesis

*Grisofulvin inhibits microtubule format thereby inhibiting cell division.

Term
Polyenes
Definition

Nystatin, Amphotericin B

*Membrane disruption

Term
Azoles
Definition
Ketocoenazole; Demethylene block of ergosterol synthesis
Term
Allyamines
Definition

Terbinatine; Squalene accumulation

*Squalene is a toxic metabolite. When it acuulates it inhibits ergosterol synthesis.

Term

Flucotyosine

*Skip, not used... Just FYI

Definition
RNA and DNA synthesis
Term
Griseofluven
Definition
Disrupts microtubules
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