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Sci Tech
Fresh approach to TB treatment
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Tests have shown that some of the azole drugs work on various mycobacteria, including the BCG strain used for inoculations and mycobacterium smegmatis, generally an opportunistic pathogen.
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A NOVEL approach to the treatment of tuberculosis (TB) has been investigated by a team of molecular geneticists in the United Kingdom, following the detection of a new gene in mycobacteria, one type of which causes the disease.
The presence of the gene opens up opportunities for the use of azole drugs which are already available for the treatment of fungal infections.
These treatments such as in Canestan and Diflucan are central to antifungal treatments of patients suffering infections such as Canadida albicans but also increasingly in internal fungal infections.
New azole drugs are being developed against fungi as the incidence of infection has increased dramatically in recent years. But the potential value of these drugs against mycobacteria had not received attention because bacteria were not thought to contain this drug target which is associated with the sterol biosynthesis pathway.
Much is known about the toxicity, side-effects, stability and penetration of tissues by azole drugs so that should help in the search for azole compounds useful against mycobacteria.
Laboratory tests have already shown that some of these drugs work on various mycobacteria, including the BCG strain that is used for inoculations and Mycobacterium smegmatis, generally an opportunistic pathogen.
The equivalent of the target of the drugs in fungi has been detected in several mycobacterial pathogens including that causing TB and the protein in the BCG strain is identical to that in M. tuberculosis causing TB. These results suggest 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 programme.
Professor Steven Kelley, of the Institute of Biological Sciences at University of Wales Aberystwyth, said:
"The sterol biosynthesis pathways are commonly found in fungi, animals and plants but this was the first that this gene had been found in bacteria. We now see the gene in several of the databases containing the genetic blueprints of different mycobacteria.
"It gives us the prospect of using existing anti-fungal compounds where there is knowledge about toxicological safety _ or at least provides strong leads for drug development — 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,'' added Professor Kelly.
Sterols are an essential component for cell growth and the best known by most people is cholesterol. But different sterols are made and used in fungi and plants.
Another part of Professor Kelly's work in tracking down a sterol, such as molecules of mycobacteria, and creating mutant bacterial genes to understand the effect of the azole drugs in detail.
These molecules stabilise the membrane, the vital interface between the inside and outside of the cells and which separates the different compartments of cells.
A large number of chemicals inhibitors of the sterol pathways have been identified in past searches and have resulted in the availability of a wide range of products used as selective anti-fungal drugs and agricultural fungicides as well as potential anti-parasitic drugs and anti-cholesterol agents for humans.
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