Thursday, 19 July 2012

Using a Yeast to Fight a Mould: The Antifungal Fungus

Growth of Pichia anomala on cereal grains
moistened with water.
The yeast Pichia anomala (a form of Candida pelliculosa) has been under investigation for its ability to drastically cut the amount of aflatoxin produced by Aspergillus flavus. This was noted when it was sprayed onto pistachio nut trees and the amount of aflatoxin fell by up to 97%. It has also been noted to be effective when sprayed onto other crops infected with other fungi.

P. anomala thus seems to be able to inhibit the growth of a range of potentially harmful fungi which is an important finding as many millions of pounds worth of crops are ruined by aflatoxin contamination, not to mention many people going hungry or even having to eat contaminated food.

How does Pichia do this? We know that on plants it can outcompete Aspergillus for food, starving it and preventing growth. There also seems to be evidence that Pichia directly sabotages Aspergillus' ability to generate the energy it needs to live and also attacks its cell wall when both are cultured together in the laboratory, so it can clearly very effectively attack Aspergillus and kill it as well as starve it.

Pichia is a eukaryotic organism as is Aspergillus (as are all fungi) and so in many ways they are very similar to each other, unlike fungi and bacteria which are quite different. When attacking a bacterium a fungus can use a whole variety of targets which will kill a bacterium but not effect the fungus - all it has to do is attack something that a bacterium uses to live or multiply but which is not present in a fungus, so the more differences there are between the two, the more targets we can use to attack the bacterium.
In a way there are similarities with the substances we humans have developed to protect us from bacterial infection as we too are eukaryotic organisms and we use antibiotics that attack bacterial cell walls (structure vitally important to bacteria but which we do not have) amongst other targets in order to treat bacterial infections.

The task of finding differences between two eukaryotic organisms to act as targets for attack is far more difficult as they are far more closely related. There are some differences (e.g. we already have antifungal drugs that attack the fungal cell wall as human cells have no similar structure) but they are in short supply.

How then does Pichia attack its close relative Aspergillus? Both have cell walls so that cannot be the target otherwise Picia would be poisoning itself! The mechanism Picia uses seems to be specific to a few filamentous fungi so may represent a mechanism we can exploit to attack Aspergillus without harming ourselves - in other words these may be targets we can exploit to make new antifungal chemicals and drugs.

Why not use Pichia itself to treat fungal infections, why bother developing expensive drugs? Unfortunately Pichia is a known human pathogen and would cause infections by itself if used directly.

Further research and development is needed but using a fungus to help fight a fungus may well lead to future breakthroughs in the treatment of several serious fungal infections, including aspergillosis.

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