Hong Kong and Beijing scientists use gene editing to find cure for superbug

A joint effort between Hong Kong and Beijing scientists has led to a breakthrough in killing a deadly superbug.

The Hong Kong research team developed a therapy that can break down the defences of the superbug Pseudomonas aeruginosa, helped by a Beijing team that provided a gene-editing method allowing scientists to test their theory, according to a paper published in the latest issue of the journal Cell Reports.

Gene editing gives scientists the ability to change an organism’s DNA, allowing genetic codes to be added, removed or modified. It makes use of scissor-like molecules that occur naturally in bacteria’s immune systems.

Pseudomonas aeruginosa is resistant to nearly all antibiotics, because of a unique defence system that can “pump” them out of its body, researchers said. Outbreaks of the infection it causes – which can occur in organs including lungs, kidneys and urinary tract, and can lead to amputation or death – are increasing worldwide.

Killer infection at Hong Kong's doorstep as city fights superbug war

Superbugs are strains of bacteria that are resistant to most antibiotics in common use. The number of Hong Kong patients diagnosed with CPE (carbapenemase-producing enterobacteriaceae), a superbug dubbed “public enemy No 1”, more than doubled from 473 cases in 2017 to 972 last year.

The Hong Kong research team, led by Dr Aixin Yan, an associate professor in biological sciences at the University of Hong Kong, found the first high-risk strain on patients in a hospital in the city in 2015, when they managed to isolate the bacteria in a laboratory. But they hit a wall soon after.

They suspected that the bacterium was protected by the pumping mechanism’s ability to get rid of antibiotics, but that this pumping also weakened the membrane. To prove this, however, they needed to remove the genes related to this function.

The team wanted to use a common gene-editing tool such as CRISPR-Cas9, but to get the scissors-like tool inside the superbug the researchers needed to bypass its super-strong defence – a challenge that is common in superbug studies. These efforts hit a wall for more than two years.

Meanwhile, Professor Xiang Hua of the Institute of Microbiology in Beijing, who co-authored the paper, had been developing a method of gene editing that gave the scissor tool what he called “a wake-up call, a GPS-like guidance”.

This research had found that many bacteria contain scissors similar to CRISPR-Cas9. These scissors can be used for gene editing from the inside, like a Trojan horse.

A collaboration between the two groups went more smoothly than expected. They quickly found an indigenous scissor inside the bacteria and turned it into a powerful tool for gene editing.

Hong Kong scientists develop antibiotic to combat superbugs

They produced new mutant species of the Pseudomonas aeruginosa superbug with modified traits in Yan’s laboratory almost every month. This allowed scientists to verify different hypotheses about the superbug’s defence mechanism, and test cures, Yan said.

“Hong Kong is an international city, where visitors come from all over the world, so we are on the front line in dealing with superbugs,” she said.

The researchers have developed a therapy combining antibiotics and a chemical agent targeting the weak spots on the membrane. The combined therapy is undergoing clinical evaluations in various hospitals, while the joint research team is turning its attentions to other superbugs.