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.
Detergent granules containing enzymes produced
by bacillus subtilis
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
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
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.
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
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
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).