1. Infective disease caused by fungi

Disease caused by fungi are on the rise in all parts of the world. This is not so much due to new agressive strains of fungi but to the fact that there are more and more immunocompromised patients: Fungi are generally rather “slow” and have little chance to overcome an intact immuno system (apart of infections of the skin, which can usually be controlled pharmacologically).

There are three large groups of immunocompromised persons: senior citizens, people having AIDS and patients being immunosupressed pharmacologically due to organ transplantations.

While there are many potent antibacterial agents and there has been enormous development on the field of antivirals in the last decade, there are very little antifungal agents that can be used to combat internal or gerneralised fungal infections. And the few available ones often have only limited effect paired with serious side effects.

2. Ergosterol biosynthesis and its inhibition

The big problem in fighting pathogenic fungi lies in the great similarity of fungal and mammalian cells. Most substances that are harmful to fungi are also harmful to the host.

One major difference between fungi and humans (apart of having two legs and being able to use the internet) is that fungi need ergosterol to grow and replicate. Ergosterol not only has the effect of moderating membrane fluidity, but also controlles several metabolic functions in the fungal cell. Although fungi can take up steroids from their environment to a certain degree, disruption of their ergosterol synthesis will always weaken their position.

The synthesis itself starts off from squalene, an open chain diterpene, and involves at least eight enzymes. There are dozends of possible intermediate and by-products. Most antifungals, both medicinal and agricultural, interfere with ergosterol biosynthesis. (For more information about antifungals and how they work you could go to doctorfungus.org)

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