Bacterial infections and acid reflux are two of the more unpleasant things that can happen to a person’s stomach. If you have suffered from those before, you are not alone as they are very common. One out of two people is infected with Helicobacter pylori, and gastric acid reflux is estimated to impact a billion people. Have you ever wondered how bacteria which causes peptic ulcers can survive in the acidic environment in your stomach? Besides risky invasive surgeries treating gastric acid reflux, is there an easier way getting rid of heartburn? You may be inspired by the following new life science research and medical technology pioneered by professors at CUHK.
Decoding H pylori’s magic trick
Infecting over 50% of population in our globe, the spiral-shaped bacteria Helicobacter pylori causes peptic ulcers and gastritis, and is associated with various types of cancer, as it is the only pathogen that can survive in the human stomach.
The stomach is a harsh environment, filled as it is with the potent gastric acid that helps us digest food. H pylori has its way to survive there. To do so, it produces urease turning the urea in the stomach into ammonia, helping it to lower the acidity. To activate the urease, the bacterium needs to use a toxic metal called nickel ions. The mystery has always been how H pylori manages to get the nickel to the urease without harming itself. Specifically, scientists were unsure how the nickel ions reached the nickel binding pocket, given that it’s located deep inside the urease protein.
Now a research team led by Professor Wong Kam-bo, CUHK’s Director and Professor in the School of Life Sciences, working with Professor Susan Lea of the University of Oxford and the US National Cancer Institute, has worked it out.
“We used electron microscopy to look into the urease and found that the helper protein complex provided us a clue about how it works,” says Professor Wong.
The helper proteins to which he refers have been developed by H pylori; the study showed that they can bind to urease and open up a tunnel in the protein complex for the nickel ions to pass through, preventing the nickel from interacting with the cell.
“The tunnel is located within the protein complex,” he says. “The nickel is delivered from the helper proteins to the active site of urease in this tunnel, so that the toxic nickel ion does not have chance to escape to the bacterial cell to induce toxicity.”
He’s now looking into ways of blocking the delivery of nickel ions to the urease, which could potentially result in new treatments for H pylori infection.
“We know that the nickel delivery can be blocked if we inhibit one of the helper proteins, UreG. We have been working on computer simulation to screen for inhibitors that could bind to UreG, so that the survival of H pylori can be reduced in an acidic environment.” He is planning to collaborate with medicinal chemists to identify those inhibitors.
Putting gastric acid in its place
Gastric acid reflux affects 14% of the global population – that’s more than a billion people. Technically known as gastroesophageal reflux disease (GERD), it happens when stomach acid flows up into the esophagus, causing irritation.
There are various ways of treating it, but they all come with drawbacks. Long-term use of medications such as proton pump inhibitors can come with side-effects, while the various surgical approaches available can be risky. Electrical stimulation of the lower esophageal sphincter (LES), the muscle at the top of the stomach, for example, works well but requires invasive surgery and implantation of devices.
A collaboration between CUHK’s Faculty of Engineering and the Faculty of Medicine, led by Professor Zhang Li from the former and Professor Philip Chiu Wai-yan and Professor Tony Chan Kai-fung from the latter, has come up with an alternative. The wirelessly powered electronic stent, or E-Stent, is a non-invasive therapy that aims to stimulate the LES without the need for invasive surgery.
It consists of a liquid metal antenna with a low melting point of 15.4℃, which means it can deform itself and be delivered through a natural orifice. The device is inserted into the patient through the mouth, removing the need for open surgery. The wearable power transfer system will generate the magnetic field to supply energy for the EStent. It is similar to the wireless charge of a mobile phone. Then, it delivers deliver electrical stimulation to the esophagus via the microneedle electrodes.
The E-Stent, which took about two years to develop, has been shown to work in trials involving pigs. In addition to the stomach, the professors hope that it might also potentially be used in other organs that feature an orifice. Work is still required to turn it into a usable clinical device, however, with human trials expected to begin in two to three years.