Gateway drug: Chinese research may open new front in war on superbugs

Chinese researchers map a 'passageway' that could offer a new route for antibiotics through the defences of drug-resistant bacteria

PUBLISHED : Sunday, 23 August, 2015, 11:44pm
UPDATED : Monday, 24 August, 2015, 5:06am

A breakthrough in biophysics could change the fight against superbugs, according to a new study by Chinese researchers.

For the first time scientists have mapped the internal structure of a secret passageway that could open up a new front in the war against deadly bacteria and render their drug resistance useless.

Scientists have known about a "back door" into the defences of nearly all bacteria for some years. The portal opened from time to time, creating a tiny passage for antibiotics to penetrate the bacteria's membrane without triggering drug resistance.

Earlier this year, a joint study by researchers from the United States and Australia reported that a new antibiotic might have gone through the portal and killed one variety of drug-resistant bacteria.

But the attempts were hit-and-miss because the researchers did not have a clear understanding of the portal's structure and the key to opening it.

The recent discovery, made by a research team led by Chinese Academy of Sciences professor Liu Zhenfeng, could significantly accelerate the development of new antibiotics that could go through the portal.

"Scientists can quickly find or design antibiotics if they know the exact structure of the targeted area. It's like travelling somewhere - it's much easier if you have a map of the place," said Liu, lead author of a paper published this month in the US journal Proceedings of the National Academy of Sciences.

"Though this is fundamental research, which is not directly linked to antibiotics development, the new knowledge may pave the way for a new strategy in our fight against superbugs."

The portal's opening and closing mechanism was previously thought similar to that of a camera's shutter, but the new research found that the structure and process was much more sophisticated.

As the portal opened, the size of the hole was controlled initially by many interlocking blades like a camera.

But as the opening became bigger, a larger structure around the blades, similar to the ribs and shaft of an umbrella, was spurred into action.

"It is incredible that nature has created such a sophisticated device at such a minuscule scale. Every movement of every part will trigger the movement of other parts. It's beautiful," Liu said.

The researchers could not observe the portal directly on living bacteria, given the structure was only five nanometres wide and well beyond the range of even the most advanced electron microscopes.

So the team had to separate the portal's protein from the rest of the membrane and cultivate it like a crystal.

By studying the shape of the large crystalline protein scientists were able to gauge the portal's structure.

It was a challenging mission, and it took Liu's team six years to realise.

After many failures, the team discovered a special enzyme that could significantly accelerate the protein's growth, helping them to expose the structure of the secret passageway in unprecedented detail.

But some nagging questions remain.

Scientists may now know that the portal can be opened and closed through external force such as a "nudge" or "stretch" on the bacteria's membrane, but they still have to work out how the portal picks up and processes the signal. It is also possible that access to the passageway is controlled by other unknown structures and mechanisms.

The portal was only found on the membrane of the bacteria. Researchers hope that further studies will lead to the development of new drugs that can penetrate the defence system of any drug-resistant microorganisms which leaving the human host in the pink of health.