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Engineered bacteria armed to fight infection

Scientists have taken a common bacteria found in the body and engineered it to a form that will seek out and destroy a potentially harmful microbe.

The team at the Nanyang Technological University in Singapore has designed harmless E. coli (Escherichia coli) bacteria that are able to detect and kill another bacteria called Pseudomonas aeruginosa which is a serious problem to some hospital patients.

The work, which is published this week in Molecular Systems Biology, is an example of the emerging field of synthetic biology - in which researchers use engineering principles to design novel living systems.

Assistant Professors Chueh Loo Poh and Matthew Wook Chang led the team that designed the new E. coli bacteria. "To our knowledge, this is the first study to use synthetic biology to tackle infectious diseases," they say.

P. aeruginosa is a bacteria which infects the digestive and respiratory tracts and is one of the leading infections acquired in hospitals. It is resistant to many antibiotics and rapidly becomes drug intolerant. For people who have compromised immune systems, such as cancer patients on chemotherapy, it has a 50 per cent mortality rate, say the researchers.

Guided missiles

Chang and Poh set out to design a guided missile in the form of an E. coli bacteria with three added 'devices' to sense, prepare a weapon and then release that weapon in response to the presence of P. aeruginosa .

The weapon used is a substance called pyocin, which is made by some bacteria to kill specific competitors, such as P. aeruginosa, while leaving E. coli unscathed.

The sensing device harnesses a system that P. aeruginosa uses to detect its own population numbers called 'quorum sensing'. Quorum sensing enables each P. aeruginosa to be aware of the presence of other P. aeruginosa microbes.

"Most microbial species have their own quorum-sensing [system]", says Poh. By putting the P. aeruginosa quorum-sensing machinery into the E. coli missile the researchers created a detection device which would notice when there were P. aeruginosa nearby.

Within the E. coli, they enabled the quorum-sensing device to act as a switch, starting pyocin production. The switch then triggers the release of pyocin from the E. coli by 'lysis', or rupture, of the cell.

Poh says that their system is far more specific than standard antibiotics. "When you have an infection and take a drug it kills all the beneficial bacteria too. In this case we are only killing the bad guys."

The researchers have demonstrated that their system works in cultures. Their next step is to test it in mice.

'Neat little system'

Professor Lars Nielsen of the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland says this is "a neat little system" and "very solid science".

He sees the potential more as a preventative "surveillance and attacking" mechanism catching P. aeruginosa in the gut rather than fighting already existing lung infections, as E. coli isn't normally found in the respiratory system.

"You would have to go through lots of regulatory hurdles before it could be used in humans," cautions Nielsen. He also raises concerns that the device genes may spread to other bacteria.

Chang and Poh point out that with the "stalled development of new antibiotics and increasing emergence of multi-drug resistant [bacteria]", this approach may become necessary. They now plan to adapt their system to tackle other pathogens such as cholera.