We owe a surprising number of scientific advances to the untidiness of scientists – penicillin, for example, might never have been discovered had Alexander Fleming thrown away his old bacterial plates before he went on holiday. The discovery of Bdellovibrio bacteriovorus was similarly fortuitous. In the 1960s Heinz Stolp was trying to isolate bacteriophages – small viruses that infect and kill bacterial cells – from soil solutions. He spread the solutions over dense lawns of Pseudomonas bacteria growing on agar plates. If phage were present in the solution, they would create small round clearings or plaques in the lawn as they killed and burst the cells they met. By the next day, no clear plaques had appeared and Stolp concluded that no phage were present. But instead of throwing away his plates, he left them on his bench.

A few days later Stolp found his old plates, and to his surprise saw clear plaques. Phage kill bacteria very quickly, so these slowly-developing plaques had to be cause by something else. When Stolp looked at the plaques under the microscope, he saw numerous small microbes whizzing around the surface of the plate and attacking the much larger Pseudomonas. Contact with this curious bug caused the Pseudomonas to burst open.

It turned out that this new microbe was also a bacterium. Over the following years Stolp and other microbiologists elucidated its behaviour and named the new species Bdellovibrio bacteriovorus. Obligate predators, Bdellovibrio cells sniff out prey cells and swim towards them. They then attach to the target cell and bore a hole in its outer membrane. Next, in a manner reminiscent of a scene from Alien, the Bdellovibrio pushes its way into the cell and divides. Its offspring eat the unfortunate host cell from the inside and finally break it open, bursting out to seek fresh prey. Gradually other, similar, species of predatory bacteria – all grouped under the generic name of vibrios – were discovered.

In recent years, microbiologists have come to realise that these fascinating bugs might have an important practical use. This is because many of the bacterial species they attack are important human pathogens, such as Salmonella, E. coli, Legionella and Pseudomonas aeruginosa. Moreover, vibrios cannot attack animal cells, do not cause an inflammatory immune response (in fact, they are common inhabitants of the human gut) and can only survive on a diet of other bacteria. This means that they could be safely introduced to the site of a bacterial infection, where they would swiftly gobble up the pathogens, exhaust their food supply and die off, leaving the host animal infection free. More importantly, documented incidences of bacteria evolving resistance to vibrio attack are vanishingly rare, and this gives vibrio therapy an enormous potential advantage over traditional antibiotics.

One researcher trying to turn this theory into a practical antibacterial therapy is Daniel Kadouri, a post-doc in George O’Toole’s lab at Dartmouth Medical School in Hanover, New Hampshire. At the recent meeting of the American Society for Microbiology, Kadouri presented the results of his work with Micavibrio. Like a microscopic leech, this bug latches onto other bacteria and sucks out their contents, and Kadouri’s team has found it to be highly effective at killing off Pseudomonas aeruginosa. This opportunistic pathogen blights patients with a reduced ability to fight infection, such as those with HIV, cancer, catheters or severe burn wounds. It also colonises the lungs of cystic fibrosis (CF) sufferers, for whom it is the main cause of illness and death. In the CF lung, aeruginosa cells grow stuck together in gloopy sheets of protein (‘biofilms‘), making them hard to shift by coughing and highly resistant to antibiotics. They are not, however, impenetrable to an assault by Micavibrio. Kadouri and his colleagues found that Micavibrio can literally decimate aeruginosa populations growing as a biofilm. 104 of 120 strains isolated from patients were susceptible to Micavibrio, suggesting potential for its use as a therapeutic agent.

Bdellovibrio is also being investigated as a possible tool in our anti-bacterial arsenal. Elizabeth Sockett’s group at the University of Nottingham, UK has been studying this species and how it too might be useful in shifting chronic aeruginosa infections. However, their work has highlighted one important issue to be overcome before doctors can happily prescribe a course of vibrio. Animals are host to numerous bacterial species, mainly harmless commensals or useful mutualists. Thus care needs to be taken that therapeutically-administered vibrio does not cause more problems than it solves by killing off our resident bacterial flora, which helps to protect is from disease and obtain nutrients from our food. In addition to this, the presence of other bacteria at an infection site might decrease the effectiveness of the vibrio onslaught against the invading pathogen. Sockett and her group introduced Bdellovibrio to more realistic ‘wound’ populations of two species: the pathogen E. coli and the harmless soil bacterium Bacillus subtilis. They found that the presence of B. subtilis significantly reduced the effectiveness of the vibrio in killing the E. coli. This means that a better understanding of microbial ecology at sites of infection is needed before vibrios can be developed into a reliable and safe antibacterial treatment.

With this caveat in mind, cautious optimism is perhaps required. However, at a time when antibiotic resistance is a growing problem there can be no doubt that new antibacterial prophylactics are sorely needed, and that the possibility of vibrios providing the next ’silver bullet’ in medicine should not be discounted.

References

Nature News article on vibrios

Review article by Elizabeth Sockett and Carey Lambert {Subscription required}