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Computation and genomics data drive bacterial research into new golden age

December 09, 2008

A potent combination of powerful new analysis methods and abundant data from genomics projects is carrying microbiology forward into a new era. Bacteria in particular are shedding light on fundamental molecular and signalling processes of interest not just within microbiology, but across the whole spectrum of life sciences embracing higher organisms, including plants and vertebrates. Medical research will benefit through improved knowledge of how bacteria behave when inside host organisms such as humans, both in benevolent symbiotic relationships and when causing infectious diseases such as TB.

But the greatest immediate interest in the field lies in the huge potential created by new methods for probing fundamental mechanisms of biology, according to Mark Buttner, who chaired a recent conference organised by the European Science Foundation (ESF) designed to bring together specialists from different fields relevant to bacterial research.

"A feeling emerged from the conference that there has never been a better time to be a microbiologist," said Buttner, who is a project leader at the John Innes Centre, an independent laboratory dedicated to plant and micro-organism research in Norwich, UK. "Rapid progress is coming about as a result of the shear amount of biological information made available by genomics and by the new and very powerful methods that are now available to analyse and predict microbial growth and behaviour systematically and quantitatively."

Already the new methods have led to a number of exciting and unexpected discoveries, some of which were revealed at the ESF conference. These related mostly to signalling processes, both at the molecular level within individual bacteria cells, and also between cells within colonies or biofilms. Some of these processes had been thought to operate only within higher organisms, in particular multi-cellular animals and plants.

For example small intracellular (within cell) signalling molecules called second messengers play a much bigger role in bacteria than had been thought. These molecules are called second messengers because they generate signals inside a cell in response to a primary external signal coming from the outside environment, such as an attack by a host immune system. As Buttner noted, second messengers were known to play an important role in complex eukaryotes, for example in controlling processes as important as vision and smell in animals. But the full role of such molecules in controlling bacterial physiology is only just being appreciated.

Even though bacteria are single celled organisms, they engage in complex relationships within communities, for example in biofilms where the cells generate a collective protective coating called the extracellular matrix. Second messengers are now being found to play a major role not just within free-living cells, but also in maintaining these communities, particularly in the face of environmental insults, such as action of a host immune system, or indeed of an antibiotic drug. Knowledge of how second messengers operate could therefore help combat bacterial infections involving biofilms, such as orthodontal disease and TB.

The conference also included presentations of fresh insights into the critical symbiotic relationships between bacteria and plants. Some plants rely on bacteria to fix the nitrogen they need for the manufacture of critical compounds, primarily proteins, from the air, rather than from nitrates they obtain in the soil. One talk by Eva Kondorosi from the Institut des Sciences du Végétal in Gif sur Yvette in France, showed that the process by which the Rhizobium bacteria in legume root nodules adapt to their nitrogen fixing role is induced, at least in part, by small peptides (proteins) made by the plant which target the bacteria in the nodule.

The ESF conference also highlighted the benefits of cross fertilisation with disciplines such as mathematics, physics and computation, that are now increasingly involved in microbiology. For example Michael Elowitz, an applied physicist from the California Institute of Technology (Caltech), showed that frequency modulation, a technique better known for its role in transmission of FM radio signals or digital data, was actually used in micro-organisms such as yeast and bacteria to orchestrate expression of many genes simultaneously involved in a particular process or pathway. Essentially the frequency of movement of a single factor initiating coordinated expression of multiple genes in turn determines the level of expression within a wide range, enabling a flexible response to different situations.

Apart from bringing together experts from different fields to reveal new insights like the role of frequency modulation in gene expression, the ESF conference also achieved its other major objective of sustaining momentum in the field by establishing BacNet as an ongoing biannual series of meetings in Europe with a similar status and quality to the Gordon conferences on microbiology in the USA. The next BACNET meeting is in planning and is likely to be held at the same location in September 2010.

European Science Foundation