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The decoding of the Bacillus subtilis genome

Detergent granules containing enzymes produced by bacillus subtilis
Following a period of patient scientific work, the 4.2 million bases making up the Bacillus subtilis genome have finally been decoded. Through their combined efforts, 28 European laboratories have helped to unveil the DNA genome sequence of this minuscule but - in scientific and industrial terms - crucially important bacterium.


Sequencing the genome of a living organism involves reconstituting the chain of millions of bases making up its genome with a view to identifying the composition of its genes. Following the deciphering of the genome of the Haemophilus influenzae bacterium in 1995, numerous teams of biologists have determined completely the sequences of a wide variety of microbial genomes. So it was that in July 1997, at the 9th International Conference on Bacilli held in Lausanne, a network of European researchers announced the sequencing of the genome of the Bacillus subtilis bacterium, so well known to biologists. This bacterium, which is several thousandths of a millimetre in length and abundantly present in nature, whether in the vicinity of plants, in the soil or in the marine environment, is totally innocuous to man and has been widely used in scientific and industrial applications for a number of years.

From experimentation to knowledge
Its capacity to develop in vitro and to produce enzymes in abundance has been put to good use mainly by the food, chemical (detergent-manufacturing) and textile industries. In fact, it constitutes a major source for the production of amylases and proteases (enzymes which catalyse the degradation of starch into simpler carbon chains, and the hydrolysis of proteins respectively). Moreover, in a medical context, this innocuous microbe, which produces proteins involved in the biosynthesis of antibiotics, is a valuable model for the study of pathogenic bacilli which resemble it closely, such as B. anthracis (responsible for anthrax, which, in its pulmonary or digestive form, is generally lethal in humans) and B. cereus (which causes food-poisoning). Lastly, B. subtilis is used as a cellular cloning vector in molecular biology laboratories.

Up to now, all these applications have relied on trial and error or, even in some cases, happy coincidence. Henceforth, as a result of the complete sequencing of the B. subtilis genome, it will be possible to identify and understand the mode of action of the

4 000 or so genes that determine the functions of the bacterium. This decoding achievement represents a valuable contribution not only to basic research but also to the development of new products, particularly in the area of drugs.

Bacillus subtilis in the spore formation phase. The oval structure in the centre is the spore, the resistant form of the bacterium.
(c) Institut Pasteur

Mobilisation on an international scale
Twenty-eight teams of European researchers from eight European Union countries (Germany, Belgium, Spain, France, the United Kingdom, Ireland, Italy and the Netherlands) have embarked on this huge sequencing operation following the completion in 1990 of a feasibility study financed by the European Commission and carried out by five of these countries. Frank Kunst and Antoine Danchin of the Pasteur Institute are responsible for coordinating all of the work, for which the Commission will have released some 4.9 million under the Biotech 1 and 2 programmes. A major contribution has been made by Japan, where seven research teams have carried out some 30% of the decoding. Swiss scientists, two American laboratories and another laboratory in Korea have also participated in this venture. In total, nearly 150 researchers have helped to identify the 4.2 million bases making up the entire genome of the bacterium. It is thanks to this huge research coordination effort that Europe has been able to accomplish this major advance.

Genetic engineering and health
"We now stand at the threshold of a new and fascinating field of research which, in its turn, will also demand a huge outlay in time and effort, since this new stage in our work, namely the identification of the function of the genes discovered, is highly complex," Frank Kunst emphasises. "Crucially, however, the genetic engineering possibilities offered by B. subtilis may prove to be particularly interesting." In addition, with a view to conducting a functional analysis of the B. subtilis genes, a group of 16 European laboratories, coordinated by Professor Ehrlich of the French National Institute for Agricultural Research (INRA), has received new financial backing of 2 million under the Biotech programme.

Already, very promising advances are being made in the task of identifying certain genes which will serve as targets for new therapeutic strategies or which will determine the production of proteins involved in the biosynthesis of antibiotics. In this way, the bacterium could constitute a source of drugs capable of taking over from existing antibiotics to which certain disease-bearing agents or emerging diseases are becoming increasingly resistant. The acquisition of genetic knowledge pertaining to B. subtilis may also help to advance our understanding of a variety of diseases caused by other related micro-organisms and will open the way for the development of new treatments.

Naturally, the industrial and commercial fall-out from the research will serve as a trigger for the European pharmaceuticals and biotechnology companies. As long ago as 1994, nine of them set up an industrial platform known as BACIP (Bacillus subtilis Industrial Platform). In keeping with the traditional role of industrial platforms, these companies, together with scientists from the research laboratories involved in the project, are conducting upstream studies in preparation for the next stage in the product marketing process. They have access to some of the results prior to publication and are examining the possibilities of submitting applications for patents (of which some fifty or so genes identified thus far are already the subject).



Project Title:  
Gene regulation for the biosynthesis of lipopeptides from Bacillus subtilis - Antifungal, antiviral and biosurfactant agents of industrial interest


Contract Reference: BIO2 CT-942051

CORDIS databaseFor more information on this project,
go to the Cordis database Record