Eaten aliveA tiny but deadly predator could offer a new way to treat persistent infections. |
Bdellovibrio recently celebrated its 40th birthday. It has been around a lot longer than that, of course, but it was discovered and named only in 1962. Although found all over the world, it remains a little-studied organism. And though tiny, it turns out to be a fascinating curiosity - and one that could have valuable medical applications.
Bdellovibrio (literally, 'curved leech') is one of the bacteria being studied by Dr Liz Sockett in the Genetics Department at the University of Nottingham. Her primary interest is in flagella, the long whip-like structures that many species of bacteria use to swim. As well as working on typical laboratory bugs, while on a visit to Oxford she was introduced to Bdellovibrio - the 'Thorpedo' of the bacterial world, able to propel itself 70-100 body lengths every second (imagine a human running at 400 mph). A pretty impressive performer, Bdellovibrio may well be the world's fastest bacterium.
This was the start of Dr Sockett's interest, but the more she learnt about Bdellovibrio the more hooked she became. "I hadn't really realised how little was known about them," she says - the entire Bdellovibrio literature amounts to only a couple of hundred papers. "I was interested in them in a very polarised way. I was interested in their flagella and how they swam, but then you begin to get all of these other questions."
The biology of the bacterium is certainly arresting. They are strong swimmers for a very good reason: they are predators, hunting down prey many times their size. They target the so-called Gram-negative bacteria, those that have two membranes shielding them from the outside world, separated by a periplasmic space.
Bdellovibrio attach to their target, burrow through the outer membrane and take up residence in the periplasmic space. There, they begin to digest the unfortunate host bacterium from within, growing into an elongated version that, says Dr Sockett, most resembles a Cumberland sausage. When the host cell has been entirely digested, the sausage breaks up, creating new baby Bdellovibrio. "Just before lysis, the infected prey cell rolls around like a football with a bag of exploding fireworks inside it," says Dr Sockett. "Then the Bdellovibrio burst out of the cell and off they go."
Postdoc Dr Carey Lambert, who carried out his PhD on Bdellovibrio in Nottingham, is equally fascinated by the bug's unusual behaviour. "There are so many features that are completely unique, have never been seen anywhere else." How does it locate its prey? What does it recognise on the prey surface? (Interactions are specific, but the nature of recognition is unknown.) How does it squeeze into the periplasmic space? (Remarkably, it seems to fuse with the outer membrane of its prey, before emerging into the periplasmic space; it even seems to pick up proteins from the outer membrane on its way through.) How are multiple infections prevented? (Once a Bdellovibrio has laid claim to a cell, no others can get in.) What controls differentiation into the sausage form and from that into the baby Bdellovibrio?
With an almost unlimited set of questions, Dr Lambert and Dr Sockett are, with Wellcome Trust support, focusing on certain key processes - particularly the mechanisms used to attack prey and the genes controlling differentiation. They will also be looking at the response of the host, and at potential mechanisms of host resistance.
The project builds on Dr Lambert's highly successful PhD, during which he established the key tools for genetic analysis of Bdellovibrio: a DNA 'library' (a complete genome broken into fragments and cloned in bacteria); a method to 'knockout' genes, to see what their biological function might be; and a luminescence assay to determine the effects of gene knockouts on the killing of prey. Armed with these tools - a fair achievement for a PhD project - Dr Lambert can begin exploring the function of other interesting-looking genes in the gene library.
With no completed genome sequence, the methods are currently a throwback to pre-genome days. While most microbiologists can enjoy searching computer databases for genes, Dr Lambert has to roll up his sleeves and get his hands dirty with the bacteria themselves. Help may be on the way, in the shape of a genome project recently initiated by Dr Stephan Schuster at the Max Planck Institute in Tübingen, with whom the Nottingham group is collaborating.
As well as its endless biological interest, Bdellovibrio may have practical applications. There is some environmental interest, as Bdellovibrio could help control bacterial populations in aquatic environments. Moreover, its prey - Gram-negative bacteria - include dangerous pathogens, such as Pseudomonas aeruginosa, which can form unsightly infections on deep burn and frostbite wounds; infections can inhibit wound healing and are notorious for developing resistance to antibiotics. Bdellovibrio won't provide a miracle cure, but it potentially could play a niche role in certain troublesome infections.
Frequently a lone pair of Bdellovibrio voices at microbiological conferences, Dr Lambert and Dr Sockett are struck by the interest shown in this obscure little microbe. Mobbed at poster sessions by curious scientists, they can point out not only that there are some extraordinary antics to examine, but that the tools are now available to study them further. Concludes Dr Sockett: "It's nice to have this grant that can capitalise on that and ask some biological questions that are relevant to disease."
External links
- Dr Liz Sockett at the University of Nottingham: Research interests

