Vitamin May Be Key to Killing Cancer-Causing Bacteria

Most people do not think much of it when they get a small cut. Simply slap on a Band-Aid and the bleeding stops in just a few minutes. However, the vitamin associated with blood clotting could hold the key to treating a bacterial infection that is often associated with stomach cancers.

Heliobacter pylori is an infectious bacterium that can be found in the gastrointestinal systems of more than half of the world’s population. According to research by the US Department of Energy (DOE) and the Oak Ridge National Laboratory, and headed by a University of Toledo biochemists, the enzyme that H. pylori uses to synthesize vitamin K2, likely holds the key to developing drugs that act against H. pylori but not against good bacteria in the stomach.

Commenting on the importance of new treatment options that would target solely H. pylori while essentially leaving other “good” stomach bacteria alone, study co-author Andrey Kovalevsky, PhD, a macromolecular crystallographer and biochemist at Oak Ridge is quoted in a press release saying, “Most drugs, including common antibiotics, use a generalized mechanism to bind to their targets which, in turn, eliminates the good bacteria you need to stay healthy as well as the bad bacteria.”

Dr. Kovalevsky’s research group used neutron analysis to study the metabolism of H. pylori, which the Centers for Disease Control and Prevention (CDC) believes is the cause for nine out of every 10 ulcers of the small intestine and esophagus, and four out of every five cases of ulcers elsewhere in the gastrointestinal system. Targeting the bacterium’s metabolism could enable scientists to develop drugs that only affect H. pylori. Although patients with H. pylori-induced ulcers usually present with stomach pain, nausea, vomiting, and even bleeding and anemia; however, most individuals with H. pylori infections do not experience any symptoms at all. The bacterium lives in the glands of the stomach lining and, being spiral shaped, “swims” through the stomach and burrows into the lining when the environment becomes too acidic. This burrowing is the root cause of most ulcers when the stomach lining becomes infected, and may be linked to stomach cancers because of the chronic inflammation this burrowing can cause.

While common ulcer treatments can help heal the stomach and relieve pain by temporarily reducing the acid levels in the stomach, they only expand the root cause of the problem, the H. pylori population. “In Europe, it is advised that patients are screened for H. pylori infections if they are going to be on proton-pump-inhibitors (PPIs) for a long time,” Manual Amieva, MD, PhD, associate professor of Pediatric Infectious Diseases and Microbiology and Immunology at Stanford University, told Contagion®. Dr. Amieva’s research focuses on the H. pylori bacterium. Her recently published findings indicate that in animal subjects, the chronic acid suppression associated with medicating the symptoms of ulcers could predispose patients to gastric cancer if they have an H. pylori infection. The constant inflammation associated with chronic ulcers that is the main symptom of an H. pylori infection is commonly associated with stomach cancers. Many scientists believe that this inflammation is what causes cancer in some patients. Although the bacterium can, once identified, be treated with antibiotics, those antibiotics often lead to other gastrointestinal issues because they kill they do not differentiate between good and bad bacteria.

According to the team’s research, published in the Proceedings of the National Academy of Sciences, H. pylori uses a unique biosynthetic pathway to synthesize vitamin K2. In humans, this vitamin plays a role in blood clotting; for the bacterium, on the other hand, it is essential to many vital chemical reactions that keep the organism alive. Interfering with the aforementioned pathway could weaken or even kill the bacteria. The enzyme HpMTAN (H. pylori 5′-methylthioadenosine nucleosidase) operates in that unique pathway and, according to movements the researchers predicted using Oak Ridge’s High Flux Isotope Reactor (HFIR), could, if targeted by a treatment, be prevented from aiding and expediting crucial reactions in the bacterial system, thereby killing the organism. The HFIR visuals enabled the researchers to observe how HpMTAN positions itself when it binds to other materials (substrates), which will allow researchers to target the enzyme and its associated reactions with medications.

Donald Ronning, PhD, a professor of biochemistry at the University of Toledo and leader of the research team, wrote that the new information “will inform future drug design efforts.” He added that this would likely take several years, but that his team’s efforts could expedite treatment development for H. pylori that would not, unlike currently available treatment options, eliminate all gastric bacteria.

H. pylori is infectious, but the exact route of transmission is not known for sure. The CDC suggests that either hand-to-mouth or mouth-to-mouth transmission of contaminated fecal matter may be the most common routes of transmission. The CDC recommends that any patient with “active gastric or duodenal ulcers or a documented history of ulcers” be tested.