Researchers have constructed a new synthetic bacterium that detects Pseudomonas aeruginosa, a common microbe and a leading cause of hospital-acquired infections, and explodes, releasing antimicrobials that kill the invaders. The results, published today (August 16) in Molecular Systems Biology, suggest that the engineered bacteria might eventually be used to prevent or treat infection with P. aeruginosa in humans.
“The paper sets up innovative use of synthetic biology for engineering microbes to carry out functions that they normally wouldn’t do”—namely, kill other bacteria, said William Bentley, chair of the Fischell Department of Bioengineering at the University of Maryland in College Park, who was not involved with the research.
P. aeruginosa is an infectious bacterium that colonizes human respiratory and gastrointestinal tracts and rapidly develops resistance to antibiotics. The bacteria cause about 10 percent of all hospital-acquired infections, and are especially common in immunocompromised patients. Infections are treated using a combination of antibiotics, but this approach also eliminates symbiotic bacteria, which may make the body more susceptible to colonization by harmful bacteria. Phage therapy, the use of specific viruses to destroy the bacteria, is another potential treatment, although it is complicated by the fact that hosts may eventually make antibodies against the virus, preventing it from killing the bacteria.
So Chueh Loo Poh and Matthew Wook Chang at Nanyang Technological University in Singapore decided to devise a new way to fight the microbe—with another bacterium. Specifically, their teams engineered Escherichia coli bacteria to detect molecules involved in P. aeruginosa quorum sensing, called acyl homoserine lactones. The release of these molecules by P. aeruginosa triggered the engineered E. coli to produce pyocin S5, a protein antibiotic that is not normally produced by E. coli and that has been shown to kill P. aeruginosa. In the process of releasing pyocin S5, the engineered bacteria burst, killing themselves.