BioWorld International Correspondent

LONDON - A bacterium that preys on other bacteria, swimming at high speeds after bacterial cells before attaching itself to their membranes and invading them, could prove to be the source of numerous new antimicrobial substances.

Molecules within the prey, which succumb to the enzymes of the predator, also might suggest new targets for the pharmaceutical industry to investigate when developing antibiotic compounds.

Those are the benefits that eventually could flow from the newly completed genomic sequence of Bdellovibrio bacteriovorus, published in the Jan. 30, 2004, issue of Science.

Stephan Schuster, head of genomics at the Max Planck Institute for Developmental Biology in Tuebingen, Germany, and senior author on the paper, told BioWorld International, "We even hope that it may be possible to train' this bacterium to attack specific pathogens."

Schuster, together with colleagues in Tuebingen and collaborators at the University of Nottingham in the UK and at Bielefeld University in Germany, reports the work in a paper titled "A Predator Unmasked: Life Cycle of Bdellovibrio bacteriovorus from a Genomic Perspective."

Schuster said the group already has sequenced the genome of a different Bdellovibrio strain, which is not predatory, and therefore he hopes to be able to identify which enzymes in B. bacteriovorus are important for entry into its prey. That work is being prepared for publication.

B. bacteriovorus is found in the soil and water in many terrestrial and aquatic ecosystems, as well as in human and animal intestines. In the free-living phase of its life cycle, it locates bacterial cells to prey on, guided by its chemosensory system. Once it has collided with a suitable prey cell, B. bacteriovorus attaches itself to the cell surface and produces a cocktail of lytic enzymes, which causes a hole to form in the victim's cell wall.

The predator then enters the space between the outer and inner membrane. At that point, Bdellovibrio can encyst, with the entry pore sealed, while the prey cell remains viable. However, usually, the predator begins to break down molecules in the cytoplasm of the prey to provide amino acids and other nutrients essential for its own growth. Eventually, the cytoplasm is completely consumed, while the cell of the predator grows. Up to 15 motile cells of B. bacteriovorus then form, which seek out and attack new prey.

Schuster said B. bacteriovorus has been studied for the past 42 years, but no one had been able to determine exactly how it accomplished such a life style. The genomic analysis of B. bacteriovorus changes that. It shows that the predatory bacterium uses a variety of lytic enzymes, which can degrade complex biopolymers of the prey, such as proteins, carbohydrates, DNA and RNA.

Schuster said: "It is clear that it does not just secrete a load of lytic enzymes harmful to everything and then take up the nutrients. Instead, it carries out a precise and orchestrated assault with multiple layers of control mechanisms that will allow fine-tuning by those who want to modulate these processes for pharmaceutical purposes."

One question the teams in Germany and UK are keen to answer: What is the host specificity of B. bacteriovorus? It does not infect eukaryotic cells.

"But we want to make sure that it does not attack useful gut bacteria in humans, or other commensal bacteria on the body," Schuster said.

There are many ways in which it might be possible to exploit the predatory microorganism, Schuster added. First, it will be important to investigate whether the lytic enzymes of B. bacteriovorus could be used as antimicrobial substances.

"Secondly, by studying this organism, we will learn which targets in pathogenic bacteria can be attacked, other than those which are already attacked by known chemical antibiotics," Schuster said. "This will allow us to identify new and interesting targets, for which the pharmaceutical industry may be able to design small-compound drugs."

Thirdly, it is possible that B. bacteriovorus could be used on its own as an antibiotic. Schuster added: "Even if this type of application in patients turns out to be too complicated, there are always other avenues to explore. For example, some groups have suggested that this bacterium could be added to meat to ensure it is free from Salmonella, or that it could be used as an additional purification step in water treatment plants, to avoid resistant bacteria breeding during sewage treatment and exchanging all their resistant genes."