Abstract
Drug resistance is a major problem for combating tuberculosis. Lack of understanding of how resistance emerges in bacteria upon drug treatment limits our ability to counter resistance. By analysis of the Mycobacterium tuberculosis interactome network, along with drug-induced expression data from literature, we show possible pathways for the emergence of drug resistance. To a curated set of resistance related proteins, we have identified sets of high propensity paths from different drug targets. Many top paths were upregulated upon exposure to anti-tubercular drugs. Different targets appear to have different propensities for the four resistance mechanisms. Knowledge of important proteins in such pathways enables identification of appropriate 'co-targets', which when simultaneously inhibited with the intended target, is likely to help in combating drug resistance. RecA, Rv0823c, Rv0892 and DnaE1 were the best examples of co-targets for combating tuberculosis. This approach is also inherently generic, likely to significantly impact drug discovery.
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Raman, K., Chandra, N. M. tuberculosis interactome analysis unravels potential pathways to drug resistance. Nat Prec (2008). https://doi.org/10.1038/npre.2008.1674.1
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DOI: https://doi.org/10.1038/npre.2008.1674.1