The presence of the gene, which is involved in the sterol biosynthesis pathway, opens up opportunities for the use of azole drugs which are already available for the treatment of fungal infections.

Laboratory tests due to be published soon in Biochemical Society Transactions 2001 have already shown that these drugs work on various mycobacteria, including the BCG strain that is used for inoculations.

These results indicate that the drugs are also likely to be active against the strains that cause infection. Further tests will confirm which of the family of azole drugs could be candidates for fast-tracking the drug discovery program.

"These surprise findings are as a direct result of analyzing the information from the mycobacterial genome project," says Professor Steven Kelly of the Institute of Biological Sciences at UWA. "The sterol biosynthesis pathway is commonly found in fungi, animals and plants, but this is the first time that this gene has been found in bacteria.

"It gives us the prospect of using existing anti-fungal compounds of accepted toxicological safety and means that these drugs could be suitable to combat TB many years before an entirely new type of drug can be discovered.

"These compounds should be considered urgently for characterisation and drug development."

Sterols are an essential component for cell growth, and a large number of chemical inhibitors of the pathway have been identified. These have resulted in the availability of a wide range of products used as selective anti-fungal drugs and fungicides as well as anti-parasitic drugs and anti-cholesterol agents for man.

These discoveries provide new opportunities for tackling the TB epidemic that is responsible for the death of more than 3 million people every year.

Inhibitors should also help to combat the increase in frequency of multi-drug resistant tuberculosis (M-DRTB) that is emerging across the globe.

Professor Kelly's work has been funded by the Biotechnology and Biological Sciences Research Council in collaboration with scientists at Vanderbilt University, Tennessee. The TB studies are being developed with clinicians at the TB reference laboratory at Llandough Hospital, Cardiff, Wales.

(References: 1. An old activity in the P450 superfamily (CYP51) and a new story of drugs and resistance. Steven L. Kelly, David C. Lamb, Michel Cannieux, Darren Greetham, Colin J. Jackson, Tim Marczylo, Cynthia Ugochukwu and Diane E. Kelly. Biochemical Society Transactions 2001 (in press). 2. A sterol Biosynthetic pathway in Mycobacterium. Lamb DC, Kelly, DE, Manning NJ, Kelly SL. FEBS Letters 1998; 437; 142-144)

11-Jul-2001