The medical community, including patients, did not want to believe that the bacterium Helicobacter pylori (H. pylori) causes ulcers. Stress was considered to be the main culprit. But in the 1980s, the Australian physician, Barry Marshall, proved that H. pylori was the cause of ulcers. To demonstrate that H. pylori was the cause of ulcers in people, not just in mice, he swallowed the bacterium and then became very sick with ulcers. He won the Nobel Prize for his discovery in 2005. Although about 50 percent of the world’s population is infected with H. pylori, only 10 to 15 percent of infections result in ulcers. But about 90 percent of ulcers and 70 percent of stomach cancer occur in people with chronic H. pylori infections according to the Centers for Disease Control and Prevention. Ulcers can be cured with antibiotics, but H pylori has become resistant to many of them. Two recent studies demonstrate the novel ways used by H. pylori to cause infections and suggest new ways to fight the ulcer-causing bacteria.
H. pylori is a scary looking bacterium. It has a corkscrew-like shape, which helps it to bore into the stomach’s lining. It has an uncanny ability to live in the acid environment of the stomach, where no other bacteria can survive. Researchers found that four proteins are required to form the corkscrew shape. They made several H. pylori mutants that lacked some of these proteins. These H. pylori mutants were unable to twist into the corkscrew shape. When the mutants were tested in mice, they were, unlike unmutated H. pylori, unable to infect and colonize the stomach of the mice. Therefore the corkscrew or helical shape of H. pylori seems to be required for infectivity. The researchers write: “Helical shape of the human pathogen Helicobacter pylori may facilitate penetration of the thick gastric mucus where it is replicated” (Sycuro, L.K. et al.).
H. pylori and vitamin B6
Researchers in Australia discovered that the enzymes necessary to make vitamin B6 are needed for H. pylori to cause infection. The researchers first looked at the genes in two types of H. pylori bacteria, ones that were very infectious or virulent and ones that had lost their ability to infect. They identified two enzymes that make vitamin B6. Human cells cannot synthesize B6. When the researchers made H. pylori mutants that lacked one of the enzymes needed to make B6, H. pylori bacteria were unable to move around and cause chronic infections in mice. Apparently, H. pylori needs B6 to effectively infect.
Targeting H .pylori
Right now the only treatments against H. pylori are antacids and antibiotics, but H .pylori has developed resistance to many antibiotics.
Only plants, fungi, and bacteria can synthesize vitamin B6. We get our vitamin B6 from food and probably also from our friendly gut bacteria, but our own cell cannot make vitamin B6. This presents a great opportunity for drug development to target the vitamin B6 synthesizing enzymes in H. pylori, called PdxA/J enzymes, to fight H. pylori. The Australian researchers write: “We therefore propose that PdxA/J enzymes may present ideal candidates for therapeutic targets against bacterial pathogen” (Grubman, A. et al.).
Interestingly, other bacteria that cause serious digestive disease like cholera and diarrhea have a similar corkscrew or helical conformation like H. pylori. So targeting one of the proteins, which help create the unusual shape, may treat a number of bacterial pathogens. “The fact that we found proteins that act on the cell wall of H. pylori that seem to be important for bacterial survival and that these proteins are found in other pathogens with similar shapes makes them a possible drug target for a number of bacterial diseases,” says Nina Salama, coauthor of the report in the journal Cell, as quoted by Science Daily.
Sycuro, L.K. et al. Peptidoglycan crosslinking relaxation promotes Helicobacter pylori’s helical shape and stomach colonization. (2010) Cell 141: 822
Grubman, A. Vitamin B6 is Required for Full Motility and Virulence in Helicobacter pylori. (2010) mBio 1: e00112