Fungi Flashcards
what does it mean that fungi are saprophytic?
secrete digestive enzymes which break down dead organic matter for nourishment (cellulase, protease, nuclease)
habitat is soil or water
what kind of pathogen does this describe?
- thick, rigid wall
- potent immunogenic
- main immunity is via neutrophils (phagocytosis)
- some considered normal flora
fungi
what are 3 unique things about the fungi cell wall that are possible drug therapies?
- chitin (fibrous)
- mannoproteins
- glucans (glucose polymers)
TLR bind fungal cell wall components
*antibiotics against peptidoglycan will be useless
what do fungi have in their cell membrane that is different than mammalian cell membranes, and can be targeted by drug therapy?
ergosterol (instead of cholesterol)
*note ergosterol is similar to cholesterol, so drugs targeting this will have toxic side effects
what are the 2 types of fungi morphology?
molds (filamentous fungi): cells elongate to form hyphae
yeast: unicellular, reproduce by budding
most fungi are dimorphic (typically mold culture at lower temp, yeast in tissues at higher temp)
what is a mass of fungi hyphae?
mycelium (pleural is mycelia)
grow by cytoplasmic extension and branching, mitotic division without cell division/separation
large fuzzy colonies in culture, usually pigmented
dimorphic fungi usually cause what level of infection?
usually systemic mycoses
filamentous mold at lower temp (culture), unicellular yeast at higher/body temp (tissue)
can also change forms based on environmental conditions
ex: Blastomyces dermatiditis, Histoplasma capsulatum
explain the basic principles of the fungi life cycle (what are the two forms of reproduction)
fungi can live as haploids or diploids, spores can reproduce and spread in environment:
fusion of haploid spores (mitotic) —> results in diploid asexual spores
sporulation of diploid spores (meiosis) —> haploid sexual spores
[sexual/asexual] fungi spores are rarely seen in clinical samples (rare among human pathogens)
sexual fungi spores are rarely seen in clinical samples (rare among human pathogens)
characteristic shape and pattern of _____, where sexual fungi spore meiosis occurs, serves as primary means of species classification
ascus (spore sac, where meiotic spores are formed)
clinical identification of fungi is by [sexual/asexual] reproduction
clinical identification of fungi is by asexual reproduction
remember that asexual spores are produced by mitosis
conidia are what kind of fungal spore?
conidia: asexual spores made outside specialized cells
sporangiosphores
sporangioshpores: asexual fungal spores made within specialized sac (sporangium)
what is the typical agar that fungi are cultured on?
Saboraud agar: broth + glucose, low pH inhibits bacteria (also antibiotics)
*note that fungi are NOT fastidious and grow best at 30C
when growing fungi on Saboraud agar, what are dematiaceous vs hyaline colonies?
dematiaceous = pigmented
hyaline = colorless
what is typically added to fungal stains, and what are 2 stains that can be used?
KOH added (kills mammalian cells, but fungi walls are resistant)
- Calcofluor white staining: fluorescent dye bind polysaccharide in fungal walls
- Methenamine silver (Grocott’s) stain: shows fungi in tissue sections
What kind of mycoses is caused by Aspergillus fumigatus?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
opportunistic
What kind of mycoses is caused by Histoplasma?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
systemic
What kind of mycoses is caused by Blastomyces?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
systemic
What kind of mycoses is caused by Coccidiodes?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
systemic
What kind of mycoses is caused by Pneumocystis jirovecci?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
opportunistic
What kind of mycoses is caused by Candida albicans?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
opportunistic
What kind of mycoses is caused by Sporothrix schenkii?
a. superficial
b. cutaneous
c. subcutaneous
d. systemic
e. opportunistic
subcutaneous
pityriasis versicolor
superficial mycoses, scaly patches of discolored skin (torso, upper arms)
yeast eating keratin in skin
piedra
superficial mycoses, fungal growth on hair shafts (eating keratin)
pityriasis versicolor vs piedra
both superficial mycoses, fungi eating keratin
pityriasis versicolor - skin
piedra - hair shafts
what kind of fungi cause cutaneous mycoses?
dermatophytes - cause lesions with inflamed rim of active infection and central clearing of healing
found everywhere, can be infectious, distinguished by micro- and macro-conidia morphology
tinia
fungal infection of keratinized tissue
distinguished by where they are found on body (ex: Tinea pedis = athlete’s foot)
what mycoses does Sporothrix schenkii cause?
Sporotrichosis (“Rose Gardener’s Disease”): subcutaneous mycoses, puncture becomes granulomatous, usually self-limiting (systemic in immunocompromised)
secondary lesions along draining lymphatics
*note Sporothrix schenckii is dimorphic - yeast form in tissue
mycetoma
subcutaneous mycoses, subcutaneous mass of fungi surrounded by granulomatous inflammation
how are systemic mycoses usually caused (acquired)?
spores inhaled from soil into lungs, can disseminate
*usually asymptomatic, except for in immunocompromised, children, elderly
where (geographically) and from what is Histoplasma capsulatum usually acquired?
central US: Ohio and Mississippi River Valleys
via spores in soil with bird droppings, conidia inhaled
how does Histoplasma capsulatum (causes systemic mycoses) proliferate in the body? what kind of immunity is required?
intracellular - multiply within macrophages
requires cell mediated immune response - granulomas form
what kind of illness does Histoplasma capsulatum cause?
systemic mycoses, usually asymptotic
otherwise acute/self-limited pulmonary illness, can present like TB
(recall Histoplasma acquired from spores in soil with bird droppings)
where (geographically) and from what is Blastomyces dermatitidis usually acquired?
Eastern US + north to Canada
microconidia in soil inhaled, but rarely disseminates from lungs
what kind of illness does Blastomyces dermatitidis cause?
about half have symptoms - fever/cough/muscle aches/chest pain/fatigue
rarely disseminates from lungs, but if so, forms ulcerated granulomas (skin, bone, GU)
how does Blastomyces dermatitidis germinate in the body?
germinate into thick wall yeast cells with unipolar broad based buds - very important for identifying in microscopy
Blastomyces - Broad Bases Buds
where (geographically) is Coccidioides immitis usually acquired, and how does it germinate in the body?
SouthWest US, Central and South America
germinate into large spherules filled with many spores, which rupture to release endospores
endospores disseminate and form new spherules
what kind of mycoses does Coccidioides immitis cause?
“Valley Fever”: fever with variable respiratory illness
if spores spread to CNS —> meningitis
usually self-limiting
what type of fungus forms yeast in infected tissue or exudates that resembles a ship steering wheel, made of multiple buds?
Paracoccidioides
Where (geographically) is paracoccidioides mycoses acquired, who is affected, and what illness does it cause?
Central and South America - mature males only (inhibited by estrogen)
causes respiratory illness, with most common secondary site being mucosa of mouth and nose —> painful/destructive lesions
what kind of mycoses do Aspergillus fumigatus, Pneumocystis jirovecci, Candida albicans, Cryptococcus neoformans, and Zygomyces cause?
opportunistic mycoses
where does Candida albicans come from and what kind of mycoses does it cause?
Candida albicans: normal flora of mucous membranes (respiratory, GI, female genital)
causes opportunistic mycoses (Candidiasis) when normal bacterial flora is diminished
*most common nosocomial pathogen
describe the clinical features of Candidiasis, caused by nosocomial Candida albicans?
invasive candidiasis enters bloodstream and disseminates, forms budding yeast and pseudohyphae in tissue and culture
—> oral thrush (raised white plaque, ulcer spreads to throat), vaginal candidiasis (white discharge, itch/burn), forms biofilm
*often sign of compromised cell mediated immunity, such as in AIDS
what is the function of the biofilm produced by Candida albicans?
Candida albicans: most common nosocomial pathogen
biofilm protects yeast from immune system/anti-fungal drugs
attaches to surfaces (human tissue, medical devices)
Germ Tube Test
screening test to differentiate Candida albicans
grow specimen in serum and germ tube forms (filamentous growth from cells, looks like a worm)
what fungi does this describe?
- found in soil containing bird droppings
- THICK polysaccharide capsule surrounding budding yeast cell
- infections start in lung, spread to brain/meninges
- opportunistic but can affect both immunocompromised and healthy patients
Cryptococcus: found in soil containing bird droppings, thick polysaccharide capsule, can spread to brain/meninges
what fungi does this describe?
- ubiquitous in environment
- only mold form
- 45* angle branching hyphae with septa
- pulmonary infection can produce fungus ball (mass of hyphae) in lung
Aspergillus: only mold form, form 45 degree branching hyphae with septa
aspergilloma: mass of hyphae in lung cavity
acute aspergillosis can be severe for immunocompromised (rarely infects healthy patients) - opportunistic
what fungi does this describe?
- ubiquitous, most adults have Ab
- causes pneumonia, NOT self-limiting (fatal if untreated)
- opportunistic via activation of dormant cysts in lungs
- cannot culture in lab
- no ergosterol in membrane
Pneumocystis jiroveci/carinii: causes Pneumocystis pneumonia (PcP or PjP) via activation of dormant cysts in lungs
—> alveoli inflammation, body produces exudate that blocks gas exchange (damage via body’s mechanisms)
how do polyenes work?
anti-fungal drugs that form pores/channels in cell membrane
ex: Amphotericin B (systemic, IV), Nystatin (topical, toxic)
what class of anti-fungal drugs form pores in the cell membrane?
Polyenes
ex: Amphotericin B (systemic), Nystatin (topical)
how do azoles work?
anti-fungal drugs that inhibit cytochrome P450-dependent enzymes involved in ergosterol biosynthesis
loss of ergosterol —> loss of membrane integrity
ex: Fluconazole, Itraconazole, Ketoconazole
*recall that ergosterol is similar to cholesterol, which is in human cell membranes, so long term use of azoles is toxic (liver toxicity)
why can’t azoles be administered long-term?
azoles: inhibit cytochrome P450-dependent enzymes involved in ergosterol biosynthesis
ergosterol is similar to cholesterol, which is in human cell membranes, so long term use of azoles is toxic (liver toxicity)
what kind of drugs are Amphotericin B and Nystatin, and what do they target?
polyenes: anti-fungal, form pores in cell membrane
Amphotericin - systemic, IV
Nystatin - topical
what kind of drugs are Fluconazole, Itraconazole, and Ketoconazole, and what do they target?
Azoles: anti-fungal, inhibit ergosterol biosynthesis
(inhibit cytochrome P450-dependent enzymes involved in ergosterol biosynthesis)
*note liver toxicity with long-term use, because ergosterol is similar to cholesterol (in human cell membranes)
what does Caspofungin do?
anti-fungal drug, inhibits glucan synthesis (disrupts cell wall)
what does 5-Fluorocytosine do?
anti-fungal drug, inhibits DNA and RNA synthesis (not used alone)
colonies that grow hyphae branching at 45* angles belong to what genus?
Aspergillus
pt is 32yo F presenting with creamy white patches lining her oral cavity. Culture from a scraping reveals budding yeast and pseudohyphae, which when suspended in plasma appear as buds with thin streaks extending from them. What fungus is this?
Candida albicans (Germ Tube Test)
pt presents with slowly-developing pneumonia and lung opacities revealed in x-ray. Stained smear of leukocytes show many tiny intracellular yeast form inclusions. What organism is this most likely to be?
Histoplasma capsulatum - tiny intracellular yeast forms in tissue, hyphae with macroconidia in culture
pt presents with pneumonia, and bronchoalveolar fluid recovered contains cysts with ring forms. What organism is likely the cause of pneumonia?
Pneumocystis carinii (P. jirovecci) - yeast, cyst in lungs
pneumonia in immunocompromised hosts
what causes Valley Fever (fever with respiratory illness)?
Coccidioides immitis - found in desert soil of SW USA
tissue morphology: large spherules with multiple endospores
culture morphology: anthroconidia (tubes)
pt is 57yo M with history of chemotherapy presenting with headache and stiff neck. CSF is centrifuged and the pellet is stained with India Ink, which reveals encapsulated yeast. What is it?
Cryptococcus neoformans: heavily encapsulated, from soil/bird droppings, lung infection that spreads to brain/meninges
what fungus is found in soil of Central & South America and causes pulmonary infections that can disseminate to mucosal mouth and nose?
Paracoccidoides braziliensis
tissue morphology: large yeast with multiple buds (“steering wheel”)
no culture morphology
