Flashcards in Medical Mycology--Kozel Deck (115)
When did fungus infections become a big deal for humans? Why was this the time of fungal blooming?
antibiotics were being used a lot-disrupt normal flora
More fungi infect plants & insects than humans--by a lot! Why do humans get away so easily?
our neutrophils do well with fungi
also our temp is relatively high at 37 degrees Celsius
**Every 1°C above 30°C excludes 6% of fungal species
What is the unique sterol found in the fungal plasma membrane?
**often targeted by anti fungal agents
Outside of the plasma membrane of the fungus is a huge cell wall. WHat is found here?
beta 1,3 glucan
beta 1,6 glucan
The content of mannoproteins can vary a lot from one fungus to another. What type of mannoprotein is found in saccharomycetes? Candida albicans? Euascomycetes?
To check for various fungal infections which component of the fungal structure is tested for?
mannoproteins--differentiate between different types of fungal infections
What is yeast?
a unicellular fungus that reproduces vegetatively by budding or fission
**doesn't reproduce sexually
What is pseudohyphae?
String of budding cells marked by constrictions rather than septa at the junctions
**can be seen in vaginitis
What is hyphae?
multicellular structures that elongate at tips by apical extension
What are coenocytic hyphae?
– hollow, multinucleate hyphae
no septa! nuclei are just floating around.
What are septate hyphae?
hyphae divided by partitions or cross-walls
What are conidia?
asexual reproductive elements (spores) produced by budding at the tip or side of a hypha
What are arthroconidia?
– asexual reproductive elements produced by fragmentation of hyphae
What are sporangiospores?
asexual spores produced inside a containing sack-like structure (sporangium)
Give some examples of asexual spores.
What is a sporangium filled with?
What do septate hyphae break apart to form?
Which part of the aspergillus is infectious?
the conidia on top of them.
What are several genera in the group mucormycetes?
What is the morphology of mucormycetes?
broad, thin walled hyphae with multiple nuclei (coenocytic), septa are rare, sporangiospores are present
What are several genera in the group basidiomycetes?
What is the morphology of basidiomycetes?
septate hyphae with clamp connections & arthroconidia
What are several genera in the group pneumocystidiomycetes?
What is the morphology of pneumocystidiomycetes?
trophic forms & cyst-like structures
What are several genera in the group saccharomycetes?
What is the morphology of saccharomycetes?
budding yeasts & hyphae
Note: saccharomyces is baker's yeast
What are some genera in the group euascomycetes?
What is the morphology of euascomycetes?
asexual conidia on specialized structures
What is the gold standard for diagnosis of a fungal infection?
difficult to do-takes skills!
days-weeks for result
has to be isolated from a normally sterile bodily fluid
What is especially awesome about a fungal culture if you can get one?
allows for sensitivity testing
How can direct microscopy be used for diagnosis of fungal infections?
scrapings-KOH to digest tissue, leave hyphae behind.
negative stain of CSF for encapsulated cryptococci--has 85% reliability
Describe how histopathology can be used to diagnose fungal infections?
body fluids & exudates used
usu need an invasive sample.
can do routine stains or special stains
Why can histopathology be dangerous when diagnosing a fungal infection?
main reason is that if a person has a fungal infection-they may very well be immunocompromised. You could introduce new problems for them by taking an invasive sample, biopsy
How can serology be used to diagnose a fungal infection?
looks for antibody to fungal antigen!
complement fixation is one immunoassay format
could reflect old infection (IgM or IgG)--esp for endemic fungi
Which fungi is serology most useful in detecting?
What are some molecular methods for diagnosis of a fungal infection?
detects nucleic acids via PCR
useful for ID of cultured fungi
difficult to use for ID in blood or tissue
Antigen detection is another way to diagnose a fungal infection. Explain this.
look @ circulating antigen
look for beta glucans (cell wall) & galactomannan (shown in aspergillosis)
How could you get a false positive when doing antigen detection for beta glucan?
beta glucan is found in gauze & other medical equipment-have to watch out.
What is a useful antigen to look for when you suspect a cryptococcosis infection?
successful antigen fungal test
What are some important anti fungal agents?
What is an example of a common azole used to treat fungal infections?
used for a lot of fungal infections
used for candida albicans & cryptococcis
wasn't used until AIDS came along.
can be taken orally-good in underdeveloped countries
**candida is developing resistance against it.
What is the structure of imidazoles-a type of azole? Give 2 examples of this type.
2 nitrogens in a ring
What is the structure of triazoles-a type of azole? Give 3 examples of this type.
3 nitrogens in a ring
What is the mechanism for azoles?
blocks ergosterol synthesis-only found in fungal plasma membrane
**inhibits lanosterol 14-alpha-demethylase
Does resistance form against azoles? What types?
target with decreased affinity for drug (enzyme less likely to bind)
efflux pump (get rid of that azole!)
over expression of target (can't overwhelm the enzyme)
What is the clinical use of ketoconazole?
limited b/c of toxicity & less efficacy
What is the clinical use of itraconazole?
broad spectrum anti fungal
What is the clinical use of voriconazole?
What is the absorption, fate & excretion of azoles?
great oral bioavailability
low protein binding
good distribution to everything, even CNS!
What are some possible side effects of azoles?
inhibitor of Cyt P450-drug interactions
What are 2 structures of allylamines?
the structure of terbinafine & naftifine
What is the mechanism of allylamine?
inhibition of squalene epoxidase
What is the clinical use of allylamines?
systemic & topical treatment of dermatophyte infection
What is the pharmacology of allylamines?
absorbed well & cleared by liver quickly
high conc'n in fatty tissue, skin, hair & nails
can be given orally
What is the structure of flucytosine?
it is a prodrug
activated when it is deaminated & becomes 5-fluorouracil in yeast cell
What is the mechanism of flucytosine?
antimetabolite-competes with uracil & inhibits DNA & RNA synthesis
What are the mechanisms of resistance against flucytosine? Is this common?
decreased uptake of drug
failure to convert the prodrug into the active form
What is the clinical use of flucytosine?
used in combo with amphotericin B in treatment of cryptococcal meningitis
Can flucytosine be used in underdeveloped countries?
no, b/c it is expensive
What is the absorption, fate & excretion of flucytosine?
taken orally-rapidly absorbed in GI
distributed in the body-good CNS penetration
excreted in urine
What is the toxicity of flucytosine?
depresses the bone marrow & can cause hepatotoxicity
What is the structure of echinocandins? What is an example of this type of anti fungal?
large, cyclic lipopeptide
What is the mechanism of echinocandins?
inhibits glucan synthesis
remember that glucan is a major part of the fungal cell wall
Is there resistance against echinocandins?
lab-altered target with decreased sensitivity
What is the clinical use of echinocandins?
used for fungi that have 1, 3 beta glucans as dominant cell wall components
ex: candida, aspergillus
used for invasive candidiasis & aspergillosis
What is the pharmacology of echinocandins?
poor oral bioavailability
extensive protein binding
can't get into the CNS well
What is the structure of polyenes? What are some major examples ?
large cyclic structure w/ a hydrophobic & hydrophilic component
Ex: amphotericin B & nystatin
often lipid formulations of amphotericin B so that you get lower toxicity & better bioavailability
What is the mechanism of amphotericin B?
direct membrane damage
Is there resistance against polyenes?
when it is present, resistance by reduced ergosterol in plasma membrane of the fungus, ergosterol with reduced binding to drug, masking of ergosterol
What is the clinical use of polyenes?
broad spectrum b/c it targets any fungus that has ergosterol in their membrane
What is the pharmacology of amphotericin B?
IV b/c not absorbed GI
w/o lipid: remains in plasma & bound to protein
w/ lipid: high plasma conc'n & therapeutic doses
not really excreted in urine
**nephrotoxicity b/c of nitrogen compounds in the blood (azotemia)-in 80% of pts
lipid formulation helps this, but HAVE to monitor renal fcn
Can amphotericin B be used in underdeveloped countries to treat fungal infections?
not often b/c it has to be given IV & it is expensive & you need extensive patient follow up to monitor for kidney damage
The patient is a 70-year-old woman with uncontrolled type 2 diabetes mellitus who presented with a one-month history of non-specific headaches associated with progressive swelling of her left eye. A diagnosis of invasive mucormycosis was made from a tissue biopsy taken from the internasal septum. She was successfully treated with intranasal and systemic amphotericin B. What is the mechanism of action of this antifungal agent?
A) Inhibits lanosterol 14-α-demethylase to block ergosterol synthesis
B) Binds to ergosterol to damage cell membranes
C) Inhibits glucan synthesis
D) Inhibitions squalene epoxidase
E) Inhibits DNA and RNA synthesis
Also, this pt had rhincerebral mucormycosis
The government of a country in Southeast Asia instituted prophylactic treatment of all AIDS patients with fluconazole to prevent development of cryptococcal meningitis. Over time, there was no increase in fluconazole resistance by Cryptococcus neoformans, but there was a dramatic increase in the resistance of Candida albicans. What is the most likely mechanism for the increased resistance to fluconazole?
A) An alteration or decrease in the amount of ergosterol in the cell membrane
B) Production of a lanosterol 14 α-demethylase with decreased affinity for the drug
C) Alterations in fungal genes that produce a failure to convert the drug into an active form
D) Alterations in genes that encode proteins involved in glucan synthesis
E) Production of squaline epoxidase with reduced binding to the drug
B. B/c that would alter the mechanism of azole drugs.
What are 3 major categories of pathogenic fungi?
superficial, cutaneous, subcutaneous mycoses
endemic mycoses-found in certain regions
Give some examples of endemic mycoses.
Give some examples of opportunistic mycoses.
What's the deal with superficial mycoses?
limited to superficial surfaces of skin & hair
only of cosmetic importance
What are some diseases caused by superficial mycoses?
Pityriasis versicolor – Malassezia furfur
Tinea nigra – Hortae werneckii
Black piedra – Piedraia hortae
White piedra – Trichosporon spp
What's the deal with cutaneous mycoses?
infections of keratinized layers of skin, hair, nails
main problem is inflammation of host
What are some fungi that cause cutaneous mycoses?
What are some diseases caused by cutaneous mycoses?
Dermatophytoses – infections of skin
Tinea unguium – infections of toes
Onychomycosis – infections of nails
What's the deal with subcutaneous mycoses?
these are infections of deep layers of skin, cornea, muscle, CT
seen in underdeveloped countries
What are some examples of fungi that cause subcu mycoses?
Hyaline molds – Acremonium spp., Fusarium spp.
Pigmented fungi – Alternaria spp., Cladosporium spp, Exophila spp.
What are some diseases caused by subcu mycoses?
Infection via traumatic inoculation
Abscess formation, nonhealing ulcers, draining sinus tracts
Localized; rarely disseminate
Describe the dimorphism of endemic mycoses.
in nature: saprobic morphology-at a lower temp.
in host: parasitic phase--in higher temp.
What does blastomyces dermatitis look like in tissue (parasitic)? What does it look like in nature (saprobic)?
parasitic: broad-based yeast
saprobic: nondescript mycelium
Where is blastomyces dermatitis found?
found in decaying organic matter in the ohio & mississippi river valleys
Which diseases are caused by blastomyces dermatitis?
extra pulmonary disease-skin, GU, CNS
disseminated disease if a pt is immunocompromised
What does histoplasma capsulatum look like in tissue (parasitic)? What does it look like in nature (saprobic)?
Tissue: intracellular budding yeast (likes to grow in phagocytic cells)
Nature: tuberculate macroconidia
Where do you find histoplasma capsulatum?
soil with high nitrogen content – bird/bat droppings
Ohio and Mississippi river valleys, Mexico, Central and South America
Which diseases does histoplasma capsulatum cause?
Acute pulmonary – 90% asymptomatic
What does coccidioides immitis aka posadasii appear like in tissue (parasitic) & in nature (saprobic)?
Parasitic: endosporulating spherule
Where is coccidioides immitis found?
soil, dust-airborne when dry
Central & S. America
Which diseases does coccidioides immitis cause?
Primary pulmonary – often asymptomatic
Disseminated – usually immunocompromised
T/F None of the endemic mycoses have man-to-man transmission.
What does penicillium marneffei look like in tissue (parasitic) & in nature (saprobic)?
parasitic: sausage-shaped yeast
saprobic: pigmented mold
Where is penicillium marneffei found?
soil, bamboo rat
Which diseases are caused by penicillium marneffei?
Disseminated infection more common in AIDS
Resembles histoplasmosis, cryptococcosis or tuberculosis
How does paracoccidioides brasiliensis appear in tissue (parasitic) & in nature (saprobic)?
parasitic: large, multiply budding yeast
saprobic: nondescript mold
Where is paracoccidioides brasiliensis found?
S & Central America
Which diseases is paracoccidioides brasiliensis associated with?
Self-limiting pulmonary disease
More common in children and immunocompromised patient
What are the highlights of aspergillus? Note: opportunistic infection.
it is everywhere in air, soil, decaying matter! You are breathing it in now!
you get infected thru inhalation of spores
it has septate, branching hyphae when it is in tissue
Which diseases does aspergillus cause?
Obstructive paranasal or bronchial (called fungus ball)
Invasive pulmonary and disseminated
At risk: Neutropenic or immunodeficient patient – BMT, solid organ transplant
High fatality rate
What are the highlights of candida? note: opportunistic
multiple species, albicans is the most common
yeast-like forms with buds, pseudohyphae & germ tubes
found in normal flora of humans
Which diseases does candida cause?
Oropharyngeal infection – thrush
Esophagitis – AIDS
What are the highlights of cryptococcus? Note: opportunistic
2 species: neoformans, gattii
ubiquitious saprophyte-found in pigeons & trees
can do an immunoassay for the capsular antigen
has a large polysaccharide capsule!
What's special about this assay that can be done for cryptococcus?
1 drop of blood
done in Africa for AIDS patients
Where does cryptococcus gattii occur?
Which diseases can be caused by cryptococcus?
pulmonary cryptococcosis-not common
opportunistic with AIDS or immunosuppression
seen in AIDS patients in underdeveloped countries
What are the highlights of mucormycosis? Note: opportunistic
aseptate coenocytic hyphae
found in soil, decaying vegetation
acquired via inhalation of spores
Which diseases can be acquired by mucormycosis?
Rhinocerebral – unique to diabetic ketoacidosis
Patients with metabolic acidosis and hematologic malignancy
What are the highlights of pneumocystis jirovecii? Note: opportunistic
can be asexual or sexual in its life cycle
tropic, sporocyst & cyst forms
cysts appear as empty, collapsed balls
main réservoir: humans!
Most people are infected with it! But it is opportunistic.
Which diseases are caused by pneumocystis jirovecii?
AIDS, immunosuppression, infants
Interstitial plasma cell pneumonitis
High mortality if untreated