Harmless bacteria re-engineered to fight a deadly strain

By Dr. Ananya Mandal, MDAug 17 2011

Scientists in Singapore have re-engineered a harmless strain of bacteria to fight another common, drug-resistant microbe that spreads in hospitals and is deadly to patients with weak immune systems.

Nazanin Saeidi and Choon Kit Wong found a new way of killing Pseudomonas aeruginosa, an opportunistic species that thrives wherever humans are weak. To fight the Pseudomonas aeruginosa bacterium, the scientists used a strain of the E.coli bacteria that is normally present in the human gut. They inserted into E.coli foreign DNA fragments that empowered it to sense the offending pathogen and quickly produce and release a deadly toxin.

This new “suicide” bacteria commonly infects hospital patients whose immune systems have taken a hit, and targets any tissue it can get a foothold on - lungs, bladders, guts - and it often causes fatal infections. Saiedi and Wong said they used a common, well-known lab bacterium Escherichia coli, or E. Coli, as a sacrificial pawn to seek and destroy this dangerous bacteria and threat to human immune systems.

Assistant professor Chueh Loo Poh, a member of the research team at the Nanyang Technological University's School of Chemical and Biomedical Engineering explained, “Once it (re-engineered E.coli) detects the presence of the aeruginosa, it produces a toxin ... and the killing molecule will be released to kill the pathogen.” Lead author of the paper, assistant professor Matthew Wook Chang said, “Our engineered bacteria inhibited the growth of the (pathogen) by 90 percent. While many antibiotics unleash a blanket attack on both good and bad bacteria, the re-engineered E.coli targets specific invaders, in this case, the P. aeruginosa.”.

The same formula can be used to redesign other microbes to fight other infective agents, such as the Vibrio cholerae which causes cholera, explained Chang. “We can easily change the sensing device,” he added. Apart from offering possible new therapies, the team believes re-engineered bacteria can be made into probiotics and consumed in food such as yoghurt. Probiotics are live bacteria that are beneficial to their hosts. The team is now testing its re-engineered E.coli on animals and hope to carry out clinical trials in people infected with Pseudomonas aeruginosa later.

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

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.

Justin Gallivan, a synthetic biologist at Emory University in Atlanta, says that the study “nicely illustrates” how synthetic bacteria can perform complex tasks. The system would also have to undergo a lot of work before it can be considered for use in humans—including, perhaps, replacing E. coli with another delivery system.

Richard Kitney, a synthetic biologist at Imperial College London said, “exposing people to E. coli is not a good thing as the bacteria are toxic outside the gut.”