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Bug busting bacterium uses genetic keep fit strategy

3 March 2011

Scientists at the University of Nottingham have shown that the predatory bacterium Bdellovibrio safeguards its hunting ability by having three pairs of a gene that helps drive its flagellar motor. The finding is part of a BBSRC-funded functional genomics project to further our understanding of this 'living antibiotic'.

  Bdellovibrio attacking E.coli

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We're all used to idea that bacteria can invade and infect our bodies. What is less well-known is that there are some bacteria which can invade and kill other bacteria, including pathogens that can cause food poisoning, wound infections and pneumonia.

Since their discovery in the 1960s (when scientists were looking to isolate bacteria-killing viruses - bacteriophages - in the search for alternatives to antibiotics), Bdellovibrio have been found in soil samples, rivers, oceans, sewage, the intestines and faeces of birds and mammals, and even in oyster shells and the gills of crabs. In fact, it is probably fair to say that Bdellovibrio are able to thrive in almost any habitat - as long as there are suitable prey.

Dinner for one?

These tiny, highly motile microbes invade and kill a wide range of pathogenic Gram-negative bacteria, including Salmonella, E. coli, Proteus, and Pseudomonas, and so there is a lot of interest in harnessing their powers as an alternative to antibiotics. Their strategy is to burrow into bacterial cells, closing up the hole behind them. Once inside, the Bdellovibrio bacterium and prey cell undergo a metamorphosis to form a bdelloplast. This allows Bdellovibrio to 'dine privately', digesting and consuming the contents of the prey cell without competition from other bacteria. When the nutrients have been exhausted, the Bdellovibrio cell divides into multiple progeny, which burst from the prey cell and swim away to continue the attack.

Professor Liz Sockett from the Institute of Genetics at the University of Nottingham has been studying the unique lifestyle of Bdellovibrio for 10 years. Her lab aims to understand all the many unusual strategies that Bdellovibrio uses to successfully invade and kill other bacteria - a rare practice amongst bacteria which mostly keep themselves to themselves. Their latest finding on the genetic control of flagellum-mediated motility in Bdellovibrio bacteriovorus appears in the February issue of the Journal of Bacteriology.

"The flagellum acts like a propeller that enables Bdellovibrio to swim towards prey-rich regions," explains Sockett. "The propeller itself is driven by a membrane-localised motor that is composed of more than 20 different structural proteins, including multiple transmembrane MotAB protein complexes."

In the latest study, Sockett and her co-workers monitored gene transcription and constructed 'paired gene deletions' as a way to examine the roles of the different motAB gene products during both intracellular growth and the free-swimming attack phase. They found that while each protein contributed to flagellum-mediated motility, no single pair of proteins was essential. But the fact that they are all transcribed throughout the intracellular cycle and the free-swimming phase has led Sockett to believe that they are beneficial to fitness.

"We think that the three motAB gene pair copies are selected for because their products ensure that predatory and free-swimming growth modes are always possible, even if natural mutations were to damage one mot gene pair," says Sockett. "This allows the bacterium to retain growth mode flexibility under conditions of changing prey availability."

Hope for new anti-bacterial therapies

The recent rise in the number of infections caused by antibiotic-resistant Gram-negative bacteria has renewed interest in alternative antimicrobial therapies. Unlike some antibiotics and unlike bacteriophage therapy, Bdellovibrio have a wide 'dietary taste' in Gram negative bacteria and will kill many species. Because they themselves are 'friendly' bacteria - they die when there are no more prey bacteria to eat and cannot infect mammalian cells - they are promising as anti-pathogens.

As a 'living antibiotic' Bdellovibrio has an added advantage that, if pathogen tries to develop resistance by adapting its genome, Bdellovibrio counter attacks by adapting its own genome. "This chess game of natural evolution has gone on unnoticed in Bdellovibrio for millions of years," says Sockett. "Understanding how Bdellovibrio has evolved to maintain its advantage could provide an alternative to directed drug discovery strategies.

"Bdellovibrio have a complex set of genes that allow them to attack and kill other bacteria and, like for these motAB genes, we are finding other key predatory processes where two or more similar genes are expressed. Evolution has tooled them up well for anti-bacterial strategies, which we may be able to use for our own benefit, whether for animal, human or crop health.

"Bdellovibrio has evolved more strategies than humans currently know to combat Gram negative bacteria successfully and it's a great privilege to work out how they do it."

Further reading

Morehouse, K.A. et al. (2011) Three motAB stator gene products in Bdellovibrio bacteriovorus contribute to motility of a single flagellum during predatory and prey-independent growth. J. Bacteriol. doi:10.1128/JB.00941-10.

Sockett, R.E. An inside job: Bdellovibrio bacteriovorus. Microbiology Today, p184-187, November 2008.

Contact

Tracey Duncombe

tel: 01793 414695
fax: 01793 413382