Only looking at a car's engine or its wheels doesn’t tell you how it drives. Similarly, looking at the metabolism or the genes of a bacterium doesn't tell scientists how it adapts.
"You have to look at the interactions of all the parts of the cell, or the car, to understand how it works," said Jörg Stelling, a biosystems engineer at the Swiss Federal Institute of Technology in Zurich.
In the March 2 issue of Science, two teams of scientists have delved into the genome of the Bacillus subtilis, a bacterium that is used to produce enzymes that have applications in biotechnology, such as washing powders and vitamins. By analyzing the bacteria's genome in more than 100 various environments, the scientists now have a better understanding of how the cell acts as a system of interacting molecular components to adapt to changing conditions.
In the first experiment, Stelling and colleagues looked at what happens when the bacteria moves from one nutrient-rich environment to another. The researchers observed the bacterium and analyzed its genome as it feasted on malate, an ionized form of malic acid. The team then moved the bacteria to a glucose-rich environment.
The results showed that the bacteria respond rapidly to malate, without large changes to the transcription process. In contrast, they adapt slower and use nearly half of their transcriptional network in response to glucose-rich environment. This response requires more work, leading to slower growth.
In the second experiment, biologist Philippe Noirot of the INRA Centre in France and his colleagues sequenced the genome of B. subtilis when they were placed in 104 different nutritional and environmental conditions. Almost every gene was differentially expressed in one or more condition, showing that the bacteria have a high transcriptional plasticity.
What was more surprising was that nearly two-thirds of B. subtilis' transcriptional plasticity is explained by the activities of sigma factors, bacterial initiation elements that bind to RNA polymerase. The experimental results suggest that these sigma factors "are the major controllers of gene expression in the cell," Noirot said.
Together, the results suggest that scientists can use the experimental design, a combination of techniques from molecular biology to bioinformatics and mathematics, to continue to unravel the complex processes of a cell as a complete system. To further that effort, the scientists have made the mathematical tools and all of their data publically available.
In the end, if scientists can understand these responses better, they might not only improve the production of enzymes but also develop new to fight infections from pathogenic bacteria, especially those that quickly develop resistance to antibiotics.
1. Buescher, J., et. al. 2012. Global network reorganization during dynamic adaptations of Bacillus subtilis metabolism. Science. 335: 1099–1103.
2. Nicolas, P., et. al. 2012. Condition-dependent transcriptome reveals high-level regulatory architecture in Bacillus subtilis. Science. 335: 1103–1106.