image

China science

Does ‘Trojan Horse’ chemical compound DHBP spell doom for world’s deadliest superbug golden staph?

Chinese team identifies compound that may be able to smuggle antibiotics past drug-resistance mechanism of Staphylococcus aureus

PUBLISHED : Monday, 28 March, 2016, 8:00am
UPDATED : Friday, 05 August, 2016, 4:59pm

A chemical that could potentially operate like a Trojan Horse by smuggling drugs through cell walls to kill off golden staph may bring an end to the long-running battle between modern science and the world’s deadliest superbug , according to a joint study by Chinese and American scientists.

Also known as Staphylococcus aureus, golden staph is a common bacterium that lives in the skin and nose.

In the United States, the human pathogen has recorded the highest death rate among all infections since 2007. If drug- resisting variants of golden staph enter a person’s bloodstream, the patient has a 33 per cent chance of dying - ten times higher than from a heart attack.

Variants of the superbug can resist a wide range of antibiotics from methicillin to vancomycin, creating infections almost everywhere in the human body that are becoming harder to treat.

The superbug has reinforced cell walls that stop the drugs which would kill it from penetrating and doing their job.

In recent years, researchers have identified a protein called WalKR that plays the role of gatekeeper by determining what enters the bug’s cell walls and what doesn’t. Teams around the world have been studying this in hope of finding a way to bypass the superbug’s drug-resistance mechanism.

Now a team led by Chinese professors Chuan He from the University of Chicago and Jiang Hualiang from the Shanghai Institute of Materia Medica, which operates under the Chinese Academy of Sciences, have identified the molecular structure of that protein. They reported their findings in the journal Nature Communications.

Guided by this structural information, they discovered - and confirmed with experiments - that a small chemical compound known as DHBP can establish a binding “handshake” with WalKR.

The chemical could therefore one day be used to kill off golden staph by effectively overriding its defences, according to Professor Yu Kunqian, another researcher with the same Shanghai institute who participated in the study.

“This discovery gives us a new, clever way of defeating the superbug,” said Yu.

Drugs could catch a “ride” inside DHBP and sneak through the golden staph’s cell walls via the gate guarded by WalKR, he explained.

One of the challenges the team found was trying to comprehend the internal structure of WalKR, which cannot be observed directly because it is tightly embedded within the cell walls.

It took the team over two years to isolate the protein and fully scrutinise its physical structure under an electron microscope.

Yu said DHBP may work for most variants of golden staph but that it will take years before the chemical can be introduced as a commercial drug.