Engineering 'good' bacteria to kill bad ones

Synthetic biology is the design and building of biological systems to improve existing functions or introduce new purposes. It draws inspiration from nature and uses materials offered by the living environment. Scientists at the Singapore Consortium for Synthetic Biology and NUS Synthetic Biology for Clinical and Technological Innovation programme tell The Straits Times about some of the exciting work they are doing in the field.

We are never alone.

Our bodies are in constant cohabitation with microbial cells. The composition of these microbial cells, an ecosystem known as the microbiome, exerts tremendous influence on our health. Just the right mix of bacteria can help to protect us from numerous chronic and acute diseases.

Recent scientific studies have highlighted the association of the microbiome with medical conditions such as obesity, infections and even depression, and have led to novel therapies. Infection by the bacterium Clostridium difficile that causes diarrhoea and more serious intestinal conditions such as colitis, for instance, can be treated by transferring the gut microbiome of a healthy person to a sick patient.

Our research team is working towards identifying the precise "good" bacteria, or probiotics, that can be used to restore function and balance in metabolic diseases such as diabetes and obesity, two pressing health concerns in Singapore.

In addition, we have developed "smart" bacteria that can deliver and release therapeutic compounds where and when they are needed in the body.

For example, we demonstrated for the first time that engineered probiotic E. coli bacteria can sense and eliminate disease-causing bacteria called Pseudomonas aeruginosa in the gut of animals.

These Pseudomonas bacteria are multidrug-resistant pathogens and are a major cause of hospital- acquired infections. When tested, the engineered E. coli bacteria were effective at clearing an established Pseudomonas infection in the gut of infected mice.

The next step is to test the engineered seek-and-kill system in humans as a next-generation antibiotic strategy that will precisely target pathogens, while minimising the damaging effect on the gut microbiota that occurs when broad- spectrum antibiotics are used. Such treatments may be very useful for reducing the incidence of multidrug-resistant bacterial infections, which represent an enormous healthcare challenge.

Associate Professor Matthew Chang, Department of Biochemistry, NUS Yong Loo Lin School of Medicine

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A version of this article appeared in the print edition of The Straits Times on June 09, 2017, with the headline Engineering 'good' bacteria to kill bad ones. Subscribe