Last post for this topic!
Show an awareness of the 3 broad classes of fungal species
The three broad classes of fungal species are yeasts, moulds and dimorphic fungi.
Yeasts are often called "sprouting fungi." They are the sorts of moulds you find if you leave an orange on the bottom of the Lost Property box for too long (yup, found this when helping to clean out the Lost Property box back in primary school). Their cells are oval-shaped and contain granules, and often vacuoles as well. They grow by forming buds which increase in size before separating out.
Moulds are what you tend to find on stale bread and so forth. They grow as multicellular filaments known as hyphae, which branch to form a dense mat called a mycelium. The three main genera of moulds are pencillum, aspergillus and mucor.
Dimorphic fungi display characteristics of yeasts or moulds, depending on temperature. They tend to be more filamentous and mould-like at lower temperatures, and more yeast-like at higher temperatures. They can grow as single cells or as rudimentary filaments known as pseudohyphae. These pseudohyphae are responsible for the invasive properties of these fungi.
Show appreciation of the four major classes of fungal infections in humans, the factors driving their rising significance, and the challenges accompanying their control with drugs.
The four major classes of fungal infections, or mycoses (singular mycosis), are simply based off where they occur. Superficial mycoses appear on the epidermis of the skin, cutaneous appear a bit deeper, subcutaneous appear in the dermal and underlying layers of the skin and systemic mycoses are very widespread. As a general rule, the deeper the mycosis is, the more severe it is. Normally, fungi do their damage by blocking things (e.g. blood vessels), rather than secreting toxins or anything like that.
Fungi normally aren't that damaging to our bodies. Most fungal infections are opportunistic infections- that is, healthy people can clear them without an issue, but they can be quite nasty towards immunocompromised individuals. This is important to note, because there are several factors that can affect a person's immune system. For example, medications such as cancer chemotherapy and corticosteroids can impair a person's immune system. Heavy antibiotic use can also worsen the impact of a fungal infection as non-pathogenic bacteria, which normally help us eliminate fungi, may be eliminated. Pre-existing conditions such as HIV/AIDS and diabetes may also increase an individual's vulnerability towards fungi.
The tricky thing about treating fungi is that they are also eukaryotic, and therefore have many more similarities to us as compared to bacteria (which are prokaryotic) and viruses (which are essentially just packages of nucleic acids). Hence, there are fewer "safe targets" for antifungal drugs. The main differences that are targeted in drug therapy are distinctive sterols in the cell membrane (we have cholesterol, whereas they have other funky things like ergosterol and lanosterol) and the fungal cell wall which is comprised of molecules called glucans.
Demonstrate awareness of 3 main classes of antifungal agents, including their basic mechanism of action, clinical uses, and most significant side-effects.
Amphotericin
Amphotericin is one of the earlier antifungal drugs. It works by binding to ergosterol, which is a sterol found only in fungal cell walls, as mentioned above. When it binds to ergosterol, it creates pores through which essential ions such as K+ can escape. This leads to death of the fungus.
Azoles
Azoles, so called because they have special rings like imidazole and triazole rings, also interfere with ergosterol. Instead of binding to ergosterol directly, however, they block an enzyme called 14-α-sterol demethylase, which converts lanosterol (another fungus-only sterol) to ergosterol. This causes depletion of ergosterol, which causes membrane dysfunction, impaired replication, and other stuff that is nasty for the fungus and good for us. (Azoles aren't that nasty though- they're fungostatic, not fungocidal, which means that they just slow down the fungus rather than kill it outright.)
Echinocandins
Echinocandins work via a different pathway altogether. They inhibit 1,3-β-D-glucan synthase (what a mouthful), which blocks the synthesis of 1,3-β-D-glucan. This is one of the glucans that is important in the synthesis of the cell wall. Hence, inhibiting this enzyme is bad for the fungus. That poor fungus.
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