Global transcriptomic response of modified Bacillus anthracis over expressing protective antigen

In this study we focused on understanding the effect of over expression of recombinant protective antigen (rPA) on the Bacillus anthracis metabolism and genes expression with the purpose of improving the production of this recombinant toxin in particular and recombinant proteins in general. To achieve this goal controlled growth of the B. anthracis ames strain transformed with pYS5 (PA producer) plasmid encoding protective antigen and the corresponding empty vector pSW4 (non-producer) were performed and protein production, bacterial growth characteristics and gene transcription pattern were analyzed. Controlled condition batch runs were performed for both strains and samples from early log (OD 3), log (OD 10) and late log (OD 16) phase were used for gene expression profiling. We found that most of the genes belonging to transport, TCA, glycolysis, PPP and amino acid biosynthesis were up-regulated in the lag phase samples which help the cell coping with the increased requirements of nutrient and energy for rPA expression. These pathways are down-regulated in the log and latelog phase as cellular stress response onsets, which is reflected in the decreased specific growth rate. Time point mRNA profiling of Bacillus anthracis ames strain BH500 transformed with pYS5 (PA producer) and the corresponding empty vector pSW4 (non-producer).