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The Pharmaceutical Journal Vol 267 No 7168 p470-481
6 October 2001

BPC 2001 summary

The M tuberculosis genome

Now that the entire genome of M tuberculosis is known, we can begin to use it to find out more about tuberculosis, said Professor Jeremy Dale from the school of biological sciences at the University of Surrey.

Knowing the bacterium’s genome might also help to establish why tuberculosis is so persistent, how resistance develops, and why BCG vaccine is not always effective. However, it was difficult to apply knowledge of the genome, because some genes might be switched on in vivo but not in vitro.

Nearly 10 per cent of the bacterium’s genome was devoted to lipid metabolism. This was probably because M tuberculosis had to be extremely hydrophilic to resist attack by macrophages and drugs. About 7 per cent of the coding capacity was for a series of related proteins whose function was unknown. Professor Dale added that the bacterium had a surprisingly large number of regulatory proteins for an opportunistic pathogen and that 28 per cent of its coding capacity was for unknown or hypothetical genes.

“Sadly, there is no one virulence gene that could be used as a target for vaccines. Many genes are involved in the bacterium’s virulence, which makes it difficult to make a useful vaccine,” he said.

Attempts had been made to determine the genes responsible for virulence by comparing the genes of M tuberculosis with those from the BCG vaccine sequence.

It was known that the BCG had deletions to its gene sequence, which was why it was attenuated. However, some of these deletions were present in infectious strains of mycobacteria, such as M bovis, so they were unlikely to be responsible for virulence. However, one area of the genome did show potential and was being explored further.

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