Tuesday, 4 December 2012

New Antifungals From Bacteria

Current antifungal drugs useful to treat aspergillosis fall into four main classes; polyenes, azoles, echinocandins and a pyrimidine analogue (Full list). All have strengths and weaknesses (some are very effective but are expensive and inconvenient to give, requiring hospital visits) and in all cases there is the potential for resistance to develop in fungal isolates, eventually rendering them useless.

 There is therefore a clear need for the continued development of new antifungal drugs. There have been several recent stories about new strategies to find new 'targets' in the fungus to attack with new drugs (1, 2) but a new source is now being reported in the media. In the history of the development of antibiotics (i.e. drugs that will kill bacteria) fungi are well represented, indeed the first antibiotic (penicillin) was discovered when a fungus started growing on Alexander Flemings' bacterial culture plates and started killing off the bacteria. We now know that many micro-organisms produce toxins though to be designed to kill off competitors for food or other valuable resource.

Bacteria can also produce powerful toxins to kill off fungi and a recent study has identified one such group of  new antifungal chemicals that they have named jagaricin. This bacterium normally lives off fungal material and is known as a 'soft rot' disease of commercial mushrooms so it was a clear candidate for the identification of chemicals that might be able to kill (and eat) fungi.

In the past researchers may have screened many strains of the bacterium and then tried to isolate the antifungal substances, identify them and subsequently isolate the genes. In the 1950's and 60's they may well have had to hunt for natural strains that produced lots of antifungal activity and then find ways to cultivate it in such a way as to enable large quantities of the new drug to be produced and purified. This was very time intensive and quite a hit or miss procedure.

 This modern research group have used techniques that are revolutionising how we can find new drugs. We can now quickly analyse an interesting new substance produced by a bacterium and 'read' its genetic structure using a Mass Spectrometer. Once we have a good idea of the genetic structure of the gene that produces the protein we can easily find it in the bacterium's genome as it ia easy to read all of the DNA in a bacterium, analyse all of the genes it contains. The gene can then be easily manipulated to produce large amounts of the interesting new gene product e.g. a new antifungal drug - a technique known as genome mining.

This revolutionary approach is already impacting many areas of drug development (and any other applicable research field including fuel production, food production etc.) and excitingly this includes  new antifungal drugs.

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