Project description:Bacterial persister cells are phenotypic variants of regular cells that are tolerant to antibiotics. Analysis of clinical isolates of M. tuberculosis showed that strains vary substantially in their tolerance to antibiotics. The level of persisters was very high is some isolates, suggesting that these are hip mutants. We investigated gene expression differences in eight clinical isolates, four of which we characterized as high-persister strains and four as low-persister, or regular, strains. Comparison of gene expression patterns may provide clues as to the genetic mechanisms underlying persister formation.
Project description:While several groups, including our own, have examined variability of M. tuberculosis at the DNA level, this is the first systematic survey of variability in mRNA expression among clinical isolates of M. tuberculosis. Genes whose expression varies among isolates when assayed under a single growth condition may make poor drug targets and vaccine antigens and may affect molecular diagnostics, so they can be used to narrow down lists of candidate molecules. Because the measurement of gene expression is extremely sensitive to environmental conditions, comparison of gene expression is labour intensive. In this study, we surveyed 12 strains. These strains are a subset of those for which we have already published genomic deletion information (Kato-Maeda et al., 2001). In order to ensure maximum reproducibility of the experiments and avoid complications caused by differences in growth conditions, we measured gene expression under well-controlled in vitro conditions. Our aims were to provide an overview of gene expression variability among clinical isolates under a single growth condition and to test whether gene functional classes are related to variability in expression. Set of arrays that are part of repeated experiments Keywords: Biological Replicate