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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Development of a suicide gene as a novel approach to killing Mycobacterium tuberculosis.

The increase in multidrug-resistant tuberculosis and high mortality among those co-infected with HIV-1 necessitates new therapeutic approaches directed at Mycobacterium tuberculosis. We hypothesized that a dominant-negative mutation in the DNA-dependent RNA polymerase gene would inhibit transcription of all genes by blocking access of the wild-type enzyme to promoters. An evolutionarily invariant lysine was substituted with arginine by site-directed mutagenesis in the rpoB gene. The dominant-negative rpoB gene product inhibited a transposon-derived kanamycin-resistance gene in both M. smegmatis and M. tuberculosis H37Rv, leading to growth inhibition of the mycobacteria on solid media containing kanamycin. The dominant-negative mutant rpoB gene is a potential suicide gene especially for the treatment of multidrug-resistant tuberculosis once a delivery strategy is also developed.[1]


  1. Development of a suicide gene as a novel approach to killing Mycobacterium tuberculosis. Rom, W.N., Yie, T.A., Tchou-Wong, K.M. Am. J. Respir. Crit. Care Med. (1997) [Pubmed]
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