2. A. fumigatus is a common member of
Ascomycota that wreaks havoc in a
person with a weakened immune
system. Spores that aren’t attacked
make their way into the alveoli of the
lungs and germinate to form
hyphae, breaking through the
epithelium in order to leech nutrients
from the vascular endothelium.
3.
4.
5. Itraconazole works by inhibiting an important xenobiotic receptor known as pregnane X receptor.
This receptor detects foreign bodies in cells, and regulates the production of xenobiotic proteins such
as CYP3A4. CYP3A4 is an enzyme responsible for converting lanosterol into ergosterol. As implied by
the name, ergosterol is a sterol used in fungal cell membranes. With itraconazole inhibiting
ergosterol, A. fumigatis can’t continue to grow.
One of the unfortunate side effects is outside drug interactions. Sick people are highly susceptible to a
fungal infection, so they’ll most likely have to take the antifungals with other medicine. Studies have
shown that azoles can act as both substrates and inhibitors for the transport protein P-
glycoprotein, or P-gp. This protein is responsible for moving exobiotics to the intestines, so toxins
and drugs alike are affected by the protein. Patients who take antifungals run the risk of messing with
their various drug dosages, since the altered levels of P-gp may remove too much or too little of the
drug being taken.
6. Amphotericin B is a polyene antifungal drug used for systemic fungal infections, such as
Aspergillosis. It’s use originated when it was discovered in the filamentous
bacteria, Strepotomyces nodusus.
Usually taken intravenously, Amphotericin B binds to the sterols found in the fungal cell
membrane called ergosterol. Here it forms a transmembrane channel causing the leakage
of intracellular monovalent ions (such as K+, Na+, H+, and Cl-). This process leads to
fungal death.
7. Caspofungin is a lipopeptide antifungal belonging to the
new class of antifungals called echinocandins. It’s
antifungal properties stem from their ability to disturb the
integrity of the fungal cell wall by inhibiting the
production of the enzyme B(1,3)-D-glucan synthase.
1,3-Beta-glucan synthase is a glucosy/transferase enzyme
involved in the generation of beta-glucan in fungi. Beta-
glucans are polysaccharides found in the fungus’s cell wall.
This leads to a decline in cell growth due to the blockade of
cell wall synthesis and a significant increase in cell death as
the cell wall loses its mechanical strength and becomes
unable to resist the intracellular osmotic pressure, leading
ultimately to destruction of the fungal cell.
