Outside In: Acquisition and analysis of large data sets promises to move us toward a greater understanding of the mechanisms by which biological systems are dynamically regulated to respond to external cues. Now, two papers explore the responses of a bacterium to changing nutritional conditions (see the Perspective by Chalancon et al. ). Nicolas et al. (p. 1103 ) measured transcriptional regulation for more than 100 different conditions. Greater amounts of antisense RNA were generated than expected and appeared to be produced by alternative RNA polymerase targeting subunits called sigma factors. One transition, from malate to glucose as the primary nutrient, was studied in more detail by Buescher et al. (p. 1099 ) who monitored RNA abundance, promoter activity in live cells, protein abundance, and absolute concentrations of intracellular and extracellular metabolites. In this case, the bacteria responded rapidly and largely without transcriptional changes to life on malate, but only slowly adapted to use glucose, a shift that required changes in nearly half the transcription network. These data offer an initial understanding of why certain regulatory strategies may be favored during evolution of dynamic control systems.

▪ Abstract The gram-positive bacterium Bacillus subtilisis capable of using numerous carbohydrates as single sources of carbon and energy. In this review, we discuss the mechanisms of carbon catabolism and its regulation. Like many other bacteria, B. subtilis uses glucose as the most preferred source of carbon and energy. Expression of genes involved in catabolism of many other substrates depends on their presence (induction) and the absence of carbon sources that can be well metabolized (catabolite repression). Induction is achieved by different mechanisms, with antitermination apparently more common in B. subtilis than in other bacteria. Catabolite repression is regulated in a completely different way than in enteric bacteria. The components mediating carbon catabolite repression in B. subtilis are also found in many other gram-positive bacteria of low GC content.

Integrative in-cell structural biology: In bacteria, RNA polymerases can associate with ribosomes to form transcription-translation units called expressomes. Multiple models based on structural data of in vitro reconstitution assays have been proposed for how the two machineries interface with one another. Understanding this bacteria-specific coupling mechanism offers insight regarding the central dogma of molecular biology and might be leveraged for antibiotic development. O'Reilly et al. found that the NusA protein interfaces between the two complexes. The authors combined cryo–electron tomography and cross-linking mass spectrometry to produce an integrative model of the transcribing, translating expressome of Mycoplasma pneumoniae obtained entirely from in-cell data. This approach contributes to the development of in-cell structural biology. Science , this issue p. 554

Living cells are made up of individual parts, i.e. the genome, the proteins, the RNA and lipid molecules as well as the metabolites and ions. However, life depends on the functional interaction among these components which is often organized in networks. Here, we present the recent development of SubtiWiki, the integrated database for the model bacterium Bacillus subtilis (http://subtiwiki.uni-goettingen.de/). SubtiWiki is based on a relational database and provides access to published information about the genes and proteins of B. subtilis and about metabolic and regulatory pathways. We have included a network visualization tool that can be used to visualize regulatory as well as protein-protein interaction networks. The resulting interactive graphical presentations allow the user to detect novel associations and thus to develop novel hypotheses that can then be tested experimentally. To facilitate the mobile use of SubtiWiki, we provide enhanced versions of the SubtiWiki App that are available for iOS and Android devices. Importantly, the App allows to link private notes and pictures to the gene/protein pages that can be synchronized on multiple devices. SubtiWiki has become one of the most complete resources of knowledge on a living organism.