Project description:The suceptibility of T. whipplei to doxycycline was investigated at the transcriptional level using a whole-genome DNA microarray. The microarray data showed good agreement with real-time quantitative PCR (R = 0.969). Exposure of T. whipplei with the subinhibitory concentration of doxycycline allowed to observe antibiotic-specific primary expression profiles, while indirect effects were detected with a 10 times higher concencentration. In contrast to what was observed for several microorganisms exposed to antibiotics, the heat-shock proteins were not affected by the exposure of T. whipplei to doxycycline. Consistent with the mode of action of this translation inhibitor, genes encoding for ribosomal proteins and translation factors were differentially transcribed. This analysis also evidenced the regulation of genes that should account for the cell growth arrest. Long-term survival of nonreplicating bacteria is likely to be ensured by an increased level of ppGpp, the nucleotide effector of the stringent response. Gene expression profile to the higher concentrations of doxycycline was mainly characterized by the up-regulation of ABC transporters that possibly form efflux and detoxification systems, through which T. whipplei may limit the effects of this bacteriostatic compound. This work represents the first comprehensive genomic approach providing insight into the expression signature triggered by the exposure of this bacterial pathogen to antibiotics. Keywords: Antibiotic stress with Doxycycline
