Fungal Pathogens Flashcards
Describe the characteristics of fungi with respect to morphology, cell composition, and biochemical functioning. Be able to explain why fungi differ from bacteria, plants, and animals.
Contain membrane-bound organelles (including nuclei)
Have rigid cell walls, which are chitinous - NO PEPTIDOGLYCAN
Cell membranes contain a particular sterol compound called ergosterol
Heterophilic (no photosynthesis) - GOTTA EAT, SON!!!
Vary widely in size
Can be unicellular or multicellular, and can reproduce sexually or asexually
Describe three means (one Linnean, two functional) for categorizing fungi. Functional categorization discriminate between: a) superficial and deep/systemic mycoses, or b) superficial fungi acquired from soil, animals or other humans.
(1) Linneus: fungi are one (Mycota) of the five kingdoms at the top of the phylogenetic classification scheme, as opposed to bacteria (Monera) or protozoa (Protista).
(2) Classification between sexually and asexually reproducing fungi.
(3) Classification between where acquired:
From soil (geophilic)
From animals (zoophilic)
From humans (anthrophilic)
Explain the differences between yeast and hyphal forms of fungi (molds), and understand that some organisms may be dimorphic.
Yeast: a uninucleated (one nucleus) growth form of fungi where the fungus reproduces asexually by budding (producing blastoconidia) or dividing in half (fission). Colonies are often creamy in texture and appearance.
Molds: a more filamentous growth form (“hyphal form”) of fungi in tubular forms, typically with a bunch of branching. Sometimes there’s superficial divisions or walls (septae) between segments. Regardless of septae, it’s still one HUGE, branched cell (though multinucleated). There’s no real separation between segments of the hyphae– cytoplasm and substances can pass back and forth.
Yeast (uninucleated) CAN show psuedohyphal forms– they’re a bunch of unicellular organisms lined up in rows (“sausage links”), but still distinct segments, unlike true hyphae.
Many (dimorphic) fungi can go back and forth between these two forms depending on environmental conditions.
[Rhizoids: little tentacle-looking forms coming off of hyphal fungal forms.]
Understand that fungi may reproduce sexually or asexually, and be able to recognize the morphology of the basic forms of asexual spores.
Asexual spores:
Conidium: can be either macro- (multinucleated) or micro- (uninucleated). Bud off of a thin arial protrusion from hyphal fungi.
Sporangium: Similar to macroconidia; lots of small asexual spores (endospores) are enclosed in a membranous sac that breaks and the entire structure is borne by a sporangiphore (later bursts and releases endospores)
Chlamydiaspores: thick-walled, round spores that are highly resistant to adverse environmental conditions. Can form at the end of hyphae (terminal) or in their middle (intercalary).
Arthrospores: develop along hyphae, but more numerous than chlamydiaspores; thick-walled, barrel-shaped spores, resemble ‘vertebrae’ in the hyphal chain.
Spherules: Like sporangia, except they don’t protrude off a little fungal extension.
Blastoconidia: Not really a spore, not sure why it’s here. This is how yeast (uninucleated) buds to divide.
Describe four means to diagnose fungal infections; Know that other advanced techniques (serological or PCR) may be used for certain infections or in specific circumstances.
Empirical: Peer at the thing. What’s it look like?
Direct examination: Look at a scraping under a microscope, stained with KOH (can use DMSO to lyse human material and leave cell walls).
Other staining techniques: India ink, chlorazol E stain.
Culture: Incubate a scraping on media. Can use special media that are antibiotic (inhibit bacterial contamination) or which turn particular colors if a certain type of fungi are added, etc. Can also use lactophenol blue to stain fungi that have already been cultured.
Tissue: Get a slice of the tissue and do histological analysis.
Use various agents (most common is PAS/D, others are calcofluor white and methenamine silver) to stain chitinous cell wells, or use mucicarmine to stain mucoid capsule.
Polyenes
Eg. Amphotericin, Nystatin
FungiCIDAL
Bind ergosterol, cause membrane to leak out important ions
Moderate to severe side effects: fever, chills.
Imidazoles/triazoles:
Eg. Ketaconazole
FungiSTATIC.
Interferes with ergosterol synthesis enzyme (14α-demethylase: lanosterol –> ergosterol).
Note: also inhibits human cholesterol synthesis very slightly. Some risk of hepatic toxicity if taken orally (inhibits CYP enzymes).
Allylamines/Benzylamines:
Eg. Terbinafine, butenafine
FungiCIDAL
Also block ergosterol synthesis by inhibiting a different enzyme(squalene epoxidase)
Byproducts begin to accumulate within the fungal cell and are toxic to it. Less risk of hepatic toxicity than imidazoles/triazoles.
Echinocandins
Eg. capsofungin
FungiCIDAL against some (Candida), fungiSTATIC against others (Aspergillus).
Inhibit the synthesis of glucan in the cell WALLS of some fungi, via inhibition 1,3-β glucan synthase.
Low toxicity, once daily dosing
Griseofulvin
Inhibits mitosis by disrupting mitotic spindle formation
FungiSTATIC
Well tolerated, used in children with TINEA CAPITIS because of its long record of safety
In many other indications it has been replaced by newer triazole medications
Flucytosine
Small molecule transported into fungal cells by cytosine permease, and is then converted by cytosine deaminase to 5-fluorouracil (5-FU).
5-FU is a pyrimidine anti-metabolite that INTERRUPTS DNA SYNTHESIS, inhibiting fungal growth.
FungiSTATIC
Ciclopirox olamine -
Chelates polyvalent metal cations (e.g. Fe and Al3+) leading to inhibition of many different fungal enzymes, including cytochromes.
Important cellular activities such as mitochondrial electron transport and energy production are inhibited.
FungiSTATIC and/or -CIDAL against a broad spectrum of fungal organisms.
