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What are the two physiological barriers for fungal growth in humans?
- Human body Temp
- Redox potential
- Body has high cellular defenses against fungal growth
What is a mesophile?
An organism that grows best at moderate temperatures
Why is it important that most fungi are mesophiles?
- They are not able to grow at 37 degrees C
- Not able to live in the human body
What redox potential is more suited for fungi than that of humans?
That of non-living organisms
Humans that develop mycoses have what characteristics?
- Poor immune status
- Environmental exposure
Describe a general Fungal infection in humans:
Why are most fungal infections mild and self-limiting in humans?
Due to high innate immunity to fungi
What features of some fungi prevent PMN phagocytosis?
Fungal proteins cause what raction in the body?
High T and B cell responses
What are the three ways that Fungi cause infections in humans?
- 1.) Unique enzymatic capacity
- 2.) Thermal dimorphism
- 3.) Cell mediated immune blocking abilities
What are the three main causes that fungi infect humans?
- 1.) Natural barriers are disturbed
- 2.) Individual is immunosuppressed
- 3.) Occupational contact
How are pathogenic mycoses classified?
By the tissue they infect
What are the six classifications of mycoses?
Where are superficial mycoses found?
Outer skin layers and hair
How do subcutaneous mycoses infections occur?
What are cutaneous mycoses called?
Where are dermatophytes found in the body?
Invade skin, hair and nails
What is the more virulent type of mycoses infection?
What mycoses type causes disease in healthy hosts?
What group of mycoses are more and more commonly causing infections?
What are characteristic problems with opportunistic mycoses infections?
- Difficult to diagnose, treat or prevent
- Becoming more and more frequent
What is an issue that must be accounted for when treating fungal infections?
Difficult to treat mycoses without toxicity to host
What is an important difference in mycoses and human cells that allows for targeted treatment with reduced host toxicity?
Ergosterol in the membrane not cholesterol
Drugs that target Erosterol in fungi compromise the host in what way?
Alter the permeability of the fungal membrane
What type of sterol is found in mycoses membranes?
What are the factors for selecting a treatment for mycoses infections?
- Agent toxicity
- Location and extent of infection
Describe the action of Azoles:
Prevent Lanosterol from being converted to Ergosterol
What prevents lanosterol from being converted to ergosterol?
What is the action of Terbinafine?
Prevents squalene from being converted to squalene epoxide (a precursor to ergosterol)
What agent prevents squalene from being converted to squalene epoxide, preventing downstream production of ergosterol?
What is the role of Flucytosine?
Kills mycoses by acting negatively on the nucleus
What is the role of Echinocandins?
Prevent B-glucan synthesis
What drug prevents B-glucan synthesis in mycoses?
What is Amphotericin B used for?
To treat serious systemic fungal infections
What drug is used to treat serious systemic fungal infections?
Describe the structure of Amphotericin B:
- Polyene lactone ring
- Saturated double bonds
What is the action of Amphotericin B?
- Binds to Ergosterol in membrane
- Alters K and Mg permeability
- Organism loses internal integrity
Can Amphotericin B penetrate the CNS?
No, too big
How is Amphotericin B used for fungal meningitis?
- Injected intrathecal
- Too big to enter the CNS systemically
Why would you inject Amphotericin B intrathecally?
To treat meningitis
What is the other name for Amphotericin B?
What is Fungizone?
Why does Amphotericin B not cause human toxicity?
It has a much lower affinity for Cholesterol than Ergosterol
Are there side effects to Amphotericin B?
Yes, many and severe
What are the side effects of Amphotericin B?